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1.
BMC Complement Med Ther ; 22(1): 203, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35907942

RESUMO

BACKGROUND: Henna (Lawsonia inermis) with anti-bacterial properties has been widely used in traditional medicine especially Persian medicine. Henna oil is suggested for diseases of infectious origin, such as cervical ulcers. Group B Streptococcus agalactiae, Pseudomonas aeruginosa and, Trichomonas vaginalis are involved in the infection of women especially cervicitis. Henna grows in dry and tropical regions. The main important landraces of henna landraces are cultivated in Kerman, Sistan and Baluchestan, Hormozgan, and Bushehr provinces in Iran. Proper use of antimicrobial agents, use of new antimicrobial strategies, and alternative methods, such as herbal methods may help reduce drug resistance in the future. This study's objective was to investigate the anti-Trichomonas vaginalis activity of three different henna landraces and antimicrobial effects against group B Streptococcus agalactiae and, Pseudomonas aeruginosa. METHODS: Total phenol content was measured by Folin ciocaltu method. Antibacterial effect of landraces of Henna against P. aeruginosa and S. agalactiae were assayed by well diffusion method and minimal inhibitory concentration assessments were done using the broth micro-dilution technique. Anti-Trichomonas effect of Henna landraces were assayed by Hemocytometery method. RESULTS: Total phenol content of Shahdad, Rudbar-e-Jonub, and Qaleh Ganj was 206.51, 201.96, and 254.85 µg/ml, respectively. Shahdad, Rudbar-e-Jonub, and Qaleh Ganj had MIC against GBS at 15, 15 and, 4 µg/ml. The growth inhibition diameter of the most effective henna (Shahdad landrace) at a concentration of 20 µg/ml on P. aeruginosa was 2.46 ± 0.15 cm and in the MIC method at a concentration of 5 µg/ml of Shahdad landrace, P. aeruginosa did not grow. IC50 of shahdad Henna after 24 h, 48 h, and 72 h was 7.54, 4.83 and 20.54 µg/ml, respectively. IC50 of Rudbar-e-Jonub extract was 5.76, 3.79 and 5.77 µg/ml in different days. IC50 of Qaleh Ganj extract was 6.09, 4.08 and 5.74 µg/ml in different days. CONCLUSIONS: The amount of total phenol in Qaleh Ganj was higher than the other varieties. In the well diffusion method, Qaleh Ganj was more effective against group B Streptococcus (Gram-positive bacterium) than the other two landraces, and Shahdad landrace was more effective against P. aeruginosa (Gram-negative bacterium) than other. In the MIC method, the same result was obtained as in the well diffusion method, but at a lower concentration.


Assuntos
Antibacterianos/farmacologia , Lawsonia (Planta) , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Feminino , Humanos , Lawsonia (Planta)/química , Fenóis , Pseudomonas aeruginosa/efeitos dos fármacos , Streptococcus agalactiae/efeitos dos fármacos , Trichomonas vaginalis/efeitos dos fármacos
2.
J Enzyme Inhib Med Chem ; 37(1): 781-791, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35193444

RESUMO

Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC50 (31)=28.72 µM (CL-B5 strain) and 33.65 µM (Y strain), IC50 (BZ)=25.31 µM (CL-B5) and 22.73 µM (Y); it lacked toxicity over mammalian cells (CC50 > 256 µM). Thiosemicarbazones 49, 51 and 63 showed remarkable trichomonacidal effects (IC50 =16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC50 ≥ 275 µM). Selenoisosters 74 and 75 presented a slightly enhanced activity (IC50=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.


Assuntos
Antiprotozoários/farmacologia , Semicarbazonas/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Semicarbazonas/síntese química , Semicarbazonas/química , Relação Estrutura-Atividade
3.
PLoS One ; 17(1): e0262242, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35061780

RESUMO

OBJECTIVES: To develop a simple DNA sequencing test for simultaneous identification and antimicrobial resistance (AMR) detection of multiple sexually transmitted infections (STIs). METHODS: Real-time PCR (qPCR) was initially performed to identify Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) infections among a total of 200 vulvo-vaginal swab samples from female sex workers in Ecuador. qPCR positive samples plus qPCR negative controls for these STIs were subjected to single gene targeted PCR MinION-nanopore sequencing using the smartphone operated MinIT. RESULTS: Among 200 vulvo-vaginal swab samples 43 were qPCR positive for at least one of the STIs. Single gene targeted nanopore sequencing generally yielded higher pathogen specific read counts in qPCR positive samples than qPCR negative controls. Of the 26 CT, NG or MG infections identified by qPCR, 25 were clearly distinguishable from qPCR negative controls by read count. Discrimination of TV qPCR positives from qPCR negative controls was poorer as many had low pathogen loads (qPCR cycle threshold >35) which produced few specific reads. Real-time AMR profiling revealed that 3/3 NG samples identified had gyrA mutations associated with fluoroquinolone resistance, 2/10 of TV had mutations related to metronidazole resistance, while none of the MG samples possessed 23S rRNA gene mutations contributing to macrolide resistance. CONCLUSIONS: Single gene targeted nanopore sequencing for diagnosing and simultaneously identifying key antimicrobial resistance markers for four common genital STIs shows promise. Further work to optimise accuracy, reduce costs and improve speed may allow sustainable approaches for managing STIs and emerging AMR in resource poor and laboratory limited settings.


Assuntos
Farmacorresistência Bacteriana/genética , Mycoplasma genitalium/genética , Neisseria gonorrhoeae/genética , Infecções Sexualmente Transmissíveis/diagnóstico , Trichomonas vaginalis/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , DNA Girase/genética , Equador , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Macrolídeos/farmacologia , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Sequenciamento por Nanoporos , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/isolamento & purificação , RNA Ribossômico 23S/química , RNA Ribossômico 23S/genética , RNA Ribossômico 23S/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Profissionais do Sexo , Infecções Sexualmente Transmissíveis/tratamento farmacológico , Infecções Sexualmente Transmissíveis/microbiologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/isolamento & purificação , Vagina/microbiologia
4.
Bioorg Med Chem ; 50: 116458, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34687983

RESUMO

Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.


Assuntos
Antiparasitários/farmacologia , Desenvolvimento de Medicamentos , L-Lactato Desidrogenase/antagonistas & inibidores , Malato Desidrogenase/antagonistas & inibidores , Animais , Antiparasitários/síntese química , Antiparasitários/química , Cryptosporidium parvum/efeitos dos fármacos , Cryptosporidium parvum/enzimologia , Humanos , L-Lactato Desidrogenase/metabolismo , Malato Desidrogenase/metabolismo , Estrutura Molecular , Testes de Sensibilidade Parasitária , Plasmodium/efeitos dos fármacos , Plasmodium/enzimologia , Schistosoma/efeitos dos fármacos , Schistosoma/enzimologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/enzimologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/enzimologia
5.
BMC Complement Med Ther ; 21(1): 265, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670535

RESUMO

BACKGROUND: Oils in traditional medicine are important products and used routinely for therapeutic purposes. Rose oil (Rosa damascene Mill), a product of Persian medicine, is advised for the treatment of Infectious diseases related to the female genitourinary tract. In the present study, R. damascena petal oil, aqueous, and hydroalcoholic extracts were evaluated for their in vitro antibacterial and anti-Trichomonas vaginalis effects. METHODS: Anti-trichomonas activity evaluation of extracts and oil were assayed by the Homocytometery method. Their antibacterial effects against Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and clinically isolated Group B Streptococcus were assayed by broth microdilution in 96-well plates. RESULTS: The MIC of hydroalcoholic and aqueous extracts ranged from 25-50 and 25-100 mg/ml, respectively. Rose oil at all administered doses failed to show any antibacterial activity. CONCLUSION: All extracts and oil concentrations showed some degree of growth inhibition activity on T. vaginalis; however, hydroalcoholic extract was more efficient.


Assuntos
Antibacterianos/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Irã (Geográfico) , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Rosa , Streptococcus/efeitos dos fármacos
6.
J Ethnopharmacol ; 281: 114554, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34438037

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Asclepias curassavica L. (Apocynaceae) is a perennial shrub used in the folk treatment of parasitism, pain, and inflammation. AIM OF THE STUDY: This work assessed the antiparasitic, anti-inflammatory, antinociceptive, and sedative effects of an ethanol extract from the aerial parts of Asclepias curassavica (ACE). MATERIALS AND METHODS: The antiparasitic activity against Trichomonas vaginalis was evaluated using the trypan blue exclusion test. The in vitro anti-inflammatory actions of ACE (1-200 µg/ml) were analyzed using LPS-stimulated primary murine macrophages. The in vivo pharmacological activity of ACE (50-200 mg/kg p.o.) was evaluated using animal models of inflammation (TPA-induced ear edema test and carrageenan-induced paw edema test) and nociception (acetic acid-induced writhing test, formalin-induced licking test, and hot plate test). RESULTS: ACE showed poor antiparasitic effects against Trichomonas vaginalis (IC50 = 302 µg/ml). ACE increased the production of IL-10 in both in vitro assays (EC50 = 3.2 pg/ml) and in vivo assays (ED50 = 111 mg/kg). ACE showed good antinociceptive actions (ED50 = 158 mg/kg in phase 1 and ED50 = 83 mg/kg in phase 2) in the formalin test. Pre-treatment with naloxone blocked the antinociceptive response induced by ACE. In addition, ACE did not induce sedative effects or motor coordination deficits in mice. CONCLUSION: Findings showed that the anti-inflammatory activity of ACE is associated with increasing levels of IL-10 in both in vitro and in vivo assays, whereas the antinociceptive effect is associated with the participation of the opioidergic system, without inducing sedation or motor coordination impairment.


Assuntos
Asclepias/química , Macrófagos Peritoneais/efeitos dos fármacos , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dor/tratamento farmacológico , Extratos Vegetais/química
7.
Biomed Pharmacother ; 139: 111611, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243597

RESUMO

Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.


Assuntos
Diaminas/farmacologia , Parasitos/efeitos dos fármacos , Peptídeo Hidrolases/metabolismo , Quinazolinas/farmacologia , Vaginite por Trichomonas/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Células 3T3 , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Chlorocebus aethiops , Feminino , Humanos , Metronidazol/farmacologia , Camundongos , Vaginite por Trichomonas/parasitologia , Células Vero
8.
Parasitol Res ; 120(6): 2233-2241, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34002261

RESUMO

Reports on metronidazole resistance of Trichomonas vaginalis strains have been on the increase. This study investigated the in vitro metronidazole resistance patterns in T. vaginalis isolates obtained from South African pregnant women and the genotypes of these isolates. This study included 362 pregnant women recruited from a hospital in Durban, South Africa. The women provided self-collected vaginal swabs for the detection of T. vaginalis by culture in Diamonds media. Cultured isolates were then subjected to anaerobic susceptibility assays to metronidazole. For the genotyping assays, the actin gene was digested by HindII, MseI, and RsaI. The banding patterns obtained after digestion was used to determine the genotypes. A total of 21/362 (5.8%) pregnant women tested positive for T. vaginalis infection. Of the 21 T. vaginalis isolates tested for metronidazole susceptibility, 9.5% (2/21) had a minimum inhibitory concentration (MIC) of 4 µg/ml (resistant), 38.1% (8/21) had a MIC of 2 µg/ml (intermediate), and 52.4% (11/21) had a MIC ≤ 1 µg/ml (susceptible). The dominant genotype that was identified across the isolates was genotype G. There was no correlation between genotype harboured and metronidazole susceptibility patterns. In this study, resistance to metronidazole was observed in clinical isolates of T. vaginalis. This study did not find a correlation between genotype harboured and metronidazole susceptibility patterns. Despite the lack of association, our study provides data on an area of research that is currently lacking in our setting.


Assuntos
Antitricômonas/farmacologia , Metronidazol/farmacologia , Vaginite por Trichomonas/parasitologia , Trichomonas vaginalis/efeitos dos fármacos , Actinas/genética , Adulto , Estudos Transversais , Resistência a Medicamentos , Feminino , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Gravidez , África do Sul , Trichomonas vaginalis/isolamento & purificação
9.
J Med Chem ; 64(10): 6608-6620, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33974434

RESUMO

Trichomonas vaginalis causes the most common, nonviral sexually transmitted infection. Only metronidazole (Mz) and tinidazole are approved for treating trichomoniasis, yet resistance is a clinical problem. The gold(I) complex, auranofin, is active against T. vaginalis and other protozoa but has significant human toxicity. In a systematic structure-activity exploration, we show here that diversification of gold(I) complexes, particularly as halides with simple C1-C3 trialkyl phosphines or as bistrialkyl phosphine complexes, can markedly improve potency against T. vaginalis and selectivity over human cells compared to that of the existing antirheumatic gold(I) drugs. All gold(I) complexes inhibited the two most abundant isoforms of the presumed target enzyme, thioredoxin reductase, but a subset of compounds were markedly more active against live T. vaginalis than the enzyme, suggesting that alternative targets exist. Furthermore, all tested gold(I) complexes acted independently of Mz and were able to overcome Mz resistance, making them candidates for the treatment of Mz-refractory trichomoniasis.


Assuntos
Antiprotozoários/química , Complexos de Coordenação/química , Ouro/química , Fosfinas/química , Animais , Antiprotozoários/metabolismo , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Modelos Animais de Doenças , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Parasitária , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Relação Estrutura-Atividade , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Tricomoníase/tratamento farmacológico , Tricomoníase/parasitologia , Trichomonas vaginalis/efeitos dos fármacos , Trofozoítos/efeitos dos fármacos
10.
Molecules ; 26(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917871

RESUMO

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan's cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.


Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Quimioinformática , Indazóis/síntese química , Indazóis/farmacologia , Antiprotozoários/química , Entamoeba histolytica/efeitos dos fármacos , Giardia lamblia/efeitos dos fármacos , Indazóis/química , Concentração Inibidora 50 , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Trichomonas vaginalis/efeitos dos fármacos , Ultrassom
11.
J Inorg Biochem ; 219: 111408, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33826972

RESUMO

Reaction of dihydroartemisinin (DHA) with 4-methyl-4'-carboxy-2,2'-bipyridine yielded the new ester derivative L1. Six novel organometallic half-sandwich chlorido Rh(III) and Ir(III) complexes (1-6) containing pentamethylcyclopentadienyl, (Cp*), tetramethylphenylcyclopentadienyl (Cpxph), or tetramethylbiphenylcyclopentadienyl (Cpxbiph), and N,N-chelated bipyridyl group of L1, have been synthesized and characterized. The complexes were screened for inhibitory activity against the Plasmodium falciparum 3D7 (sensitive), Dd2 (multi-drug resistant) and NF54 late stage gametocytes (LSGNF54), the parasite strain Trichomonas vaginalis G3, as well as A2780 (human ovarian carcinoma), A549 (human alveolar adenocarcinoma), HCT116 (human colorectal carcinoma), MCF7 (human breast cancer) and PC3 (human prostate cancer) cancer cell lines. They show nanomolar antiplasmodial activity, outperforming chloroquine and artemisinin. Their activities were also comparable to dihydroartemisinin. As anticancer agents, several of the complexes showed high inhibitory effects, with Ir(III) complex 3, containing the tetramethylbiphenylcyclopentadienyl ligand, having similar IC50 values (concentration for 50% of maximum inhibition of cell growth) as the clinical drug cisplatin (1.06-9.23 µM versus 0.24-7.2 µM, respectively). Overall, the iridium complexes (1-3) are more potent compared to the rhodium derivatives (4-6), and complex 3 emerges as the most promising candidate for future studies.


Assuntos
2,2'-Dipiridil/química , Artemisininas/química , Artemisininas/farmacologia , Irídio/química , Compostos Organometálicos/química , Ródio/química , Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Humanos , Compostos Organometálicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Trichomonas vaginalis/efeitos dos fármacos
12.
Bioorg Med Chem Lett ; 37: 127843, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556576

RESUMO

A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2-12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated.


Assuntos
Antiparasitários/farmacologia , Indazóis/farmacologia , Tricomoníase/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Antiparasitários/síntese química , Antiparasitários/química , Relação Dose-Resposta a Droga , Resistência a Medicamentos/efeitos dos fármacos , Indazóis/síntese química , Indazóis/química , Estrutura Molecular , Relação Estrutura-Atividade , Tricomoníase/parasitologia
13.
Parasitol Res ; 120(1): 233-241, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33073325

RESUMO

Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most prevalent non-viral sexually transmitted infection that affects over 170 million people worldwide. The only type of drug recommended for the therapeutic control of trichomoniasis is the 5-nitroimidazoles, although there have been reports of some undesirable side effects and clinical resistance. Hence, the need for the search for new tricomonicidal agents is necessary. In a previous work, we demonstrated that two 2-amino-4-aryl thiazole derivatives (ATZ-1 and ATZ-2) possess a portent antigiardial effect. In the current paper, we investigated the in vitro antitrichomonal activity of these thiazole compounds. Both ATZ-1 and ATZ-2 reduced the viability and growth of parasites in a dose-dependent manner, with an IC50 value of 0.15 µg/mL and 0.18 µg/mL, respectively. Furthermore, both thiazole compounds were able to decrease the proteolytic activity in T. vaginalis trophozoites compared with untreated parasites. Interestingly, a full proteolytic inhibition profile was observed in the 50-kDa region which was associated with the decreased expression of the gene that codes for the trichomonad protease TvMP50. The docking simulations predicted strong interactions of the thiazole compounds in the TvMP50 protease's active site, suggesting a possible role as protease inhibitors. Our results demonstrate the potential of 2-amino-4-aryl thiazole derivatives as trichomonicidal compounds and could be, mechanistically, involved in the inhibition of key trichomonad proteases.


Assuntos
Antitricômonas/farmacologia , Inibidores de Proteases/farmacologia , Tiazóis/farmacologia , Tricomoníase/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Parasitária , Tricomoníase/parasitologia
14.
Int J STD AIDS ; 32(1): 89-91, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33121364

RESUMO

Metronidazole desensitization is recommended in patients with trichomoniasis and history of an allergic reaction to metronidazole due to presumed cross reactivity with tinidazole and lack of reliably safe and effective alternative therapies. We report our experiences in a patient with persistent trichomoniasis who failed to complete metronidazole desensitization due to a burning sensation over her whole body and pruritus but was later successfully desensitized to tinidazole without experiencing any adverse effects.


Assuntos
Antitricômonas/farmacologia , Antitricômonas/uso terapêutico , Metronidazol/efeitos adversos , Tinidazol/uso terapêutico , Tricomoníase/tratamento farmacológico , Trichomonas vaginalis/efeitos dos fármacos , Adulto , Resistência a Medicamentos , Feminino , Humanos , Hipersensibilidade , Resultado do Tratamento , Trichomonas vaginalis/isolamento & purificação
15.
Molecules ; 25(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202696

RESUMO

Trichomoniasis, is the most prevalent non-viral sexually transmitted disease worldwide. Although metronidazole (MDZ) is the recommended treatment, several strains of the parasite are resistant to MDZ, and new treatments are required. Curcumin (CUR) is a polyphenol with anti-inflammatory, antioxidant and antiparasitic properties. In this study, we evaluated the effects of CUR on two biochemical targets: on proteolytic activity and hydrogenosomal metabolism in Trichomonas vaginalis. We also investigated the role of CUR on pro-inflammatory responses induced in RAW 264.7 phagocytic cells by parasite proteinases on pro-inflammatory mediators such as the nitric oxide (NO), tumor necrosis factor α (TNFα), interleukin-1beta (IL-1ß), chaperone heat shock protein 70 (Hsp70) and glucocorticoid receptor (mGR). CUR inhibited the growth of T. vaginalis trophozoites, with an IC50 value between 117 ± 7 µM and 173 ± 15 µM, depending on the culture phase. CUR increased pyruvate:ferredoxin oxidoreductase (PfoD), hydrogenosomal enzyme expression and inhibited the proteolytic activity of parasite proteinases. CUR also inhibited NO production and decreased the expression of pro-inflammatory mediators in macrophages. The findings demonstrate the potential usefulness of CUR as an antiparasitic and anti-inflammatory treatment for trichomoniasis. It could be used to control the disease and mitigate the associated immunopathogenic effects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antiparasitários/uso terapêutico , Curcumina/uso terapêutico , Terapia de Alvo Molecular , Compostos Fitoquímicos/uso terapêutico , Tricomoníase/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antiparasitários/farmacologia , Curcumina/farmacologia , Citocinas/genética , Citocinas/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Óxido Nítrico/biossíntese , Parasitos/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Proteólise/efeitos dos fármacos , Piruvato Sintase/genética , Piruvato Sintase/metabolismo , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tricomoníase/parasitologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/enzimologia , Trichomonas vaginalis/genética
16.
Parasitol Res ; 119(12): 4197-4204, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068149

RESUMO

Resistance mechanisms of Trichomonas vaginalis to metronidazole are still not well understood. It has been shown that Mycoplasma hominis has the ability to establish an endosymbiotic relationship with T. vaginalis. This study investigated the association between T. vaginalis and M. hominis symbiosis in relation to metronidazole resistance. This study included 362 pregnant women from the King Edward VIII hospital in South Africa. The women provided self-collected vaginal swabs for the diagnosis of T. vaginalis by culture. Metronidazole susceptibility using the broth-microdilution assay was performed. Detection of the 16S rRNA from M. hominis using T. vaginalis genomic DNA as the template was performed. All statistical analysis was conducted in R statistical computing software. A total of 21 culture positive isolates were obtained resulting in a prevalence of 5.8% for T. vaginalis in the study population. Under anaerobic incubation, 52.4% (11/21) of the isolates were susceptible to metronidazole (MIC ≤ 1 µg/ml). Intermediate resistance (MIC of 2 µg/ml) and full resistance (4 µg/ml) was observed in 38.1% (8/21) and 9.5% (2/21) of the isolates, respectively. The majority of the isolates 95% (19/20) were susceptible to metronidazole under aerobic conditions. Only one isolate had a MIC of 50 µg/ml. M. hominis was shown to be present in 85.7% (18/21) of the T. vaginalis isolates. However, there was no significant association between metronidazole susceptibility and T. vaginalis-M. hominis symbiosis. This study provides evidence of emerging metronidazole resistance in T. vaginalis. However, these resistance profiles were not associated with M. hominis symbiosis.


Assuntos
Resistência a Medicamentos , Metronidazol/farmacologia , Mycoplasma hominis/fisiologia , Simbiose , Trichomonas vaginalis/microbiologia , Adulto , Antiprotozoários/farmacologia , Feminino , Humanos , Mycoplasma hominis/isolamento & purificação , Testes de Sensibilidade Parasitária , Gravidez , África do Sul/epidemiologia , Vaginite por Trichomonas/epidemiologia , Vaginite por Trichomonas/microbiologia , Vaginite por Trichomonas/parasitologia , Trichomonas vaginalis/efeitos dos fármacos
17.
J Infect Dev Ctries ; 14(9): 1054-1064, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33031096

RESUMO

INTRODUCTION: The present study aimed to determine the chemical compositions and bioactivities of the essential oil of Atalantia sessiflora Guillaumin (A. sessiflora), including antibacterial, antimycotic, antitrichomonas, anti-inflammatory and antiviral effects. METHODOLOGY: The essential oil from leaves of A. sessiflora was extracted by hydrodistillation using a Clevenger apparatus. Chemical compositions of oil were identified by GC/MS. Antimicrobial and antitrichomonas activity were determined by the microdilution method; anti-inflammatory and antiviral were determined by the MTT method. RESULTS: The average yield of oil was 0.46 ± 0.01% (v/w, dry leaves). A number of 45 constituents were identified by GC/MS. The essential oil comprised four main components. The oil showed antimicrobial activities against Gram-positive strains as Staphylococcus; Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli; and finally four Candida species. Enterococcus faecalis and Pseudomonas aeruginosa were least susceptible to the oil of A. sessiflora, as seen in their MIC and MLC values over 16% (v/v). Activity against Trichomonas vaginalis was also undertaken, showing IC50, IC90 and MLC values of 0.016, 0.03 and 0.06% (v/v) respectively, after 48 hours of incubation. The oil of A. sessiflora displayed activity against the nitric oxide generation with the IC50 of 95.94 ± 6.18 µg/mL. The oil was completely ineffective against tested viruses, ssRNA+, ssRNA-, dsRNA, and dsDNA viruses. CONCLUSIONS: This is the first yet comprehensive scientific report about the chemical compositions and pharmacological properties of the essential oil of A. sessiflora. Further studies should be done to evaluate the safety and toxicity of A. sessiflora oil.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antitricômonas/farmacologia , Bactérias/efeitos dos fármacos , Óleos Voláteis/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Antitricômonas/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Óxido Nítrico/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células RAW 264.7 , Rutaceae/química , Vietnã , Vírus/efeitos dos fármacos
18.
BMC Complement Med Ther ; 20(1): 271, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907567

RESUMO

Human trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.


Assuntos
Organismos Aquáticos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Infecções por Protozoários/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Animais , Feminino , Humanos , Estrutura Molecular , Óleos Voláteis/química , Extratos Vegetais/química , Plantas Medicinais , Trichomonas vaginalis/efeitos dos fármacos , Tritrichomonas foetus/efeitos dos fármacos
19.
J Infect Dev Ctries ; 14(7): 793-799, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32794472

RESUMO

INTRODUCTION: Trichomoniasis is a worldwide sexually transmitted disease caused by Trichomonas vaginalis. It inflicts severe complications to the human genitourinary system. The devastating negative effects and the emergence of resistance to common medication impose the search for safer and effective alternatives. This research aimed to investigate the effect of the Allium sativum, Nigella sativa crude extracts (NsCE) and the combination between their most effective doses with metronidazole. METHODOLOGY: Vaginal swabs were obtained from symptomatic patients, and cultured on Diamond's medium. Assessment of various concentrations of these herbs at different follow-up periods was done by counting the number of dead T. vaginalis trophozoites using the hemocytometer and trypan blue staining. Transmission electron microscope study was done. RESULTS: NsCE 9 mg/mL yielded the highest lethal effect on T. vaginalis trophozoites after 72 hours, compared with metronidazole. Combination of NsCE 9 mg/mL and metronidazole 50 µg/mL gave the best result. Additionally, Tomex90 µg/mL, represents a tolerable effect after 72 hours, but metronidazole 100 µg/mL still has higher effect. These results were confirmed by the ultrastructural changes observed in T. vaginalis trophozoites, signifying severe damage of nucleus and cytoplasm with large vacuolization and cell membrane defects. CONCLUSIONS: NsCE is a promising anti-Trichomonas especially its combination with metronidazole which showed a high synergistic effect.


Assuntos
Antiprotozoários/farmacologia , Extratos Vegetais/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Alho/química , Humanos , Metronidazol/farmacologia , Nigella sativa/química , Testes de Sensibilidade Parasitária , Plantas Medicinais , Infecções Sexualmente Transmissíveis/parasitologia , Fatores de Tempo , Vaginite por Trichomonas/parasitologia , Trichomonas vaginalis/crescimento & desenvolvimento , Trichomonas vaginalis/ultraestrutura , Vagina/parasitologia
20.
Curr Drug Targets ; 21(16): 1672-1686, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753007

RESUMO

Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to inflammation of the vulva and/or vagina due to the presence of pathogens that cause trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Several discomforts are associated with these infections, as well as pregnancy complications and the facilitation of HIV transmission and acquisition. The increasing resistance of microorganisms to drugs used in therapy is remarkable, since women report the recurrence of these infections and associated comorbidities. Different resistant mechanisms already described for the drugs used in the therapy against Trichomonas vaginalis, Candida spp., and Gardnerella vaginalis, as well as aspects related to pathogenesis and treatment, are discussed in this review. This study aims to contribute to drug design, avoiding therapy ineffectiveness due to drug resistance. Effective alternative therapies to treat vaginitis will reduce the recurrence of infections and, consequently, the high costs generated in the health system, improving women's well-being.


Assuntos
Resistência Microbiana a Medicamentos/fisiologia , Vaginite/tratamento farmacológico , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Feminino , Humanos , Tricomoníase/tratamento farmacológico , Tricomoníase/microbiologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/microbiologia , Vaginite/microbiologia
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