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1.
Biotechnol Lett ; 43(5): 1005-1018, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515159

RESUMO

Streptomyces is one of the most prolific producers of economically important bioactive compounds used against several illnesses; it has also been found to produce industrially useful enzymes. In this study, Streptomyces sp. (ERINLG-201) was isolated from the soil sample of Kodanad forest (Southern Western Ghats), The Nilgiris, Tamil Nadu, India. ERINLG-201 isolate showed promising antibacterial activity against tested Gram-positive and Gram-negative bacteria which was confirmed by perpendicular 'T' streak method. Secondary metabolites of ERINLG-201 isolate exhibited promising antibacterial activity against tested Gram-positive and Gram-negative bacteria which was confirmed by disc diffusion method using the ethylacetate extract. Further, the ethylacetate extract of ERINLG-201 (15 g) was packed in column chromatography over silica gel and eluted; it resulted in isolation of a new naphthoquinone derivative named bluemomycin from the active fraction. Bluemomycin showed promising antibacterial activity against Gram-negative bacteria and clinical isolates at least concentration (6.25 µg/mL). Cytotoxic studies of bluemomycin showed promising activity against A549, Skvo-3 and HepG2 cell lines with IC50 values of 5.9, 24.2 and 11 µM, respectively.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Naftoquinonas/farmacologia , Streptomyces/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA Bacteriano/genética , Florestas , Fungos/efeitos dos fármacos , Humanos , Índia , Testes de Sensibilidade Microbiana , Naftoquinonas/química , Naftoquinonas/metabolismo , Filogenia , RNA Ribossômico 16S/genética , Microbiologia do Solo , Streptomyces/classificação , Streptomyces/genética , Streptomyces/isolamento & purificação
2.
Iran J Vet Res ; 20(4): 308-312, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32042298

RESUMO

BACKGROUND: Duck rearing is one of the important livelihoods of rural people. Duck plague is one of the diseases causing heavy mortality resulting in economic losses. CASE DESCRIPTION: An outbreak of duck plague in a farm in Kadavakathi Village near Tenkasi, Tirunelveli Dt., is reported. FINDINGS/TREATMENT AND OUTCOME: Two thousands out of 4500 Chara-Chemballi breed of ducks which were recently purchased from Chenganacherry in Kerala died, with a mortality rate of 44.4%. Clinical signs of inappetence, partial closure of eyelid, conjunctivitis, corneal opacity, oculo-nasal discharge, soiled vent with green white watery diarrhoea, ataxia, incoordination and sudden death were observed. Necropsy examination revealed diphtheritic membrane in the oesophagus, congestion, petechial haemorrhages and multifocal gray white areas on the surface of the liver, epicardial haemorrhages, congested trachea, lung, kidneys, splenomegaly with mottled appearance and enteritis. Microscopical examination revealed presence of eosinophilic intranuclear and intracytoplasmic inclusions in the epithelial cells of the intestine and hepatocytes, degeneration and necrosis of enterocytes, dilated crypt epithelial cells with presence of eosinophilic intranuclear and intracytoplasmic inclusions, congestion and lymphoid cell depletion in the spleen, vasculitis, congestion, and haemorrhages in the trachea and lungs, proventriculitis, and congested kidneys. Polymerase chain reaction (PCR) also confirmed the duck plague viral infection by the amplification of polymerase gene fragment (446 bp). CONCLUSION: Based on the above findings, the Chara-Chemballi duck disease outbreak was diagnosed as duck viral enteritis infection.

3.
J Parasit Dis ; 42(2): 315-320, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29844638

RESUMO

A total of 120 tissue samples (Rumen, reticulum, omasum, abomasum, small intestine and large intestine) were collected from slaughter houses in Chennai, Kanchipuram and Tiruvallur districts and five samples from necropsy room at Department of Veterinary Pathology, Madras Veterinary College, Chennai, Tamil Nadu. Overall prevalence of GI parasites was 52.00%. Among the positive samples, single infection was found to be more (53.84%) than themixed infection (46.15%). Out of which, oesophagostomosis was 17.00% and found as single infection. In oesophagostomosis, significant gross lesions observed in the small and large intestine were multiple small to large, round to irregular, hard, fibrotic, raised nodules. The wall of the large intestine was greatly thickened and oedematous and the nodules were seen projecting into the lumen and mucosal surface was intact. On histopathological examination, ileum of sheep showed parasitic nodules with central baso-eosinophilic necrotic area, larval stages in the necrotic area, surrounded by layers of inflammatory cells and finally encapsulated in a thick fibrous connective tissue capsule. Immunohistochemistry (IHC) with Vimentin showed intense cytoplasmic positive signals DAB Brown. PCR was carried out targeting ITS2 regions of the O. columbianum and O. venulosum. DNA isolated from both the faecal eggs and adult worms showed good amplification.

4.
J Photochem Photobiol B ; 181: 59-69, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29510357

RESUMO

A novel one-dimensional coordination polymer containing Cu(I)Cu(II) core with chloro bridge on Cu(I) and ligand bridge on Cu(II) ions (1) and a mononuclear Cu(II) complex (2) have been synthesized from the reactions of 3- and 4-methoxy-3-quinolin-3-ylimino-methyl-2-phenol with [CuCl2(PPh3)2]. The ligands and the complexes have been characterized by spectral and analytical methods. In addition, the structures of both the ligands and the copper complexes were confirmed by single crystal X-ray diffraction studies. In both complexes, the phenolic oxygen and azomethine nitrogen atom of the ligand coordinate to the copper ions in a monobasic bidentate manner resulting in an approximately square planar geometry around the copper ion. In the polymeric complex, the N atom of the quinoline ring is coordinated to Cu(I) in addition to the phenolic oxygen and azomethine nitrogen atom coordinating to Cu(II) ion, thus bridging Cu(I) and Cu(II) ions in the complex. The interactions of the compounds with calf thymus DNA (CT-DNA) have been followed by absorption and emission titration methods, which revealed that the compounds interact with CT-DNA through intercalation. Further, the interactions of the compounds with bovine serum albumin (BSA) were also investigated using UV-visible, fluorescence spectroscopic methods. The results indicated that complex 1 exhibited a stronger binding to CT-DNA and BSA than the free ligands and complex 2. In addition, the in vitro cytotoxicity experiment showed that complexes 1 and 2 exhibit potent cytotoxic properties against PANC-1and Hela cells. Moreover, while complex 1 showed prominent cytotoxic activity against both PANC-1 and Hela cells with IC50 of 17.91 and 11.67 µM, complex 2 showed moderate cytotoxic activities with IC50 of 25.13 and 16.41 µM in PANC-1 and Hela cells. Further, apoptosis was confirmed by fluorescence image using EB/AO reagent.


Assuntos
Complexos de Coordenação/síntese química , Cobre/química , Animais , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Cloretos/química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Clivagem do DNA/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Células HeLa , Humanos , Ligantes , Microscopia de Fluorescência , Conformação Molecular , Ligação Proteica , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Espectrofotometria , Viscosidade
5.
Biomed Pharmacother ; 93: 796-806, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28715864

RESUMO

One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0.40 and 0.39mM at 24h when compared to other tested cells, respectively. Apoptosis was confirmed by annexin V-FITC/PI kit using flow cytometry and confocal microscope in MOLM-14 and NB-4 cells. In addition, 2-acetyl-benzylamine induced cell cycle arrest at G2/M phase in MOLM-14 cells and G0/G1 phase in NB-4 cells. Apoptosis mechanism was confirmed by RT-PCR and Western blot analysis. Treatment with 2-acetyl-benzylamine decreased the Bcl-2 activity and increased the Bax expression; cytochrome c was released and caspases-3 was activated in MOLM-14 and NB-4 cells. Besides, 2-acetyl-benzylamine inhibited the expression of JAK2/STAT3 in MOLM-14 and NB-4 cells. In vivo administration of 2-acetyl-benzylamine inhibited the growth of MOLM-14 cells in xenograft mice model. Molecular docking study has been performed to investigate the binding mode and to estimate the binding energy of 2-acetyl-benzylamine with the active site of JAK-2, AKT1, FLT3 and Bcl-2. The above findings proved that 2-acetyl-benzylamine could be developed as a potential therapeutic agent against cancer.


Assuntos
Acetofenonas/farmacologia , Antineoplásicos/farmacologia , Benzilaminas/farmacologia , Justicia/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Células HL-60 , Humanos , Janus Quinase 2/metabolismo , Células Jurkat , Células K562 , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismo
6.
J Parasit Dis ; 41(2): 473-475, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28615862

RESUMO

Onchocerca gibsoni subcutaneous nodules in four cross bred Jersey cows aged 5-6 years brought for post mortem with calcified and caseated skin nodules in the lateral flank region is reported. Examination and dissection of these nodules revealed that they were "worm nests" of Onchocerca sp. of filarid nematodes. The worm nests were carefully dissected and filarid worms were extracted out. Multiple numbers of worms were recovered from each nodule ranging from 15 to 20. Female worms were found inside the worm nests and were found to be filled with microfilariae. The nodules weighed 2-3 g. Based on the morphological features the worms were identified as O. gibsoni.

7.
J Parasit Dis ; 41(2): 510-513, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28615869

RESUMO

Coenurosis is a disease of the central nervous system in sheep. A survey was carried out to assess the occurrence of Coenurus cerebralis in Madras red sheep. A prevalence rate of 12.30 % observed when 122 slaughtered Madras red sheep were examined in an organized farm during 2002 to 2007 at Livestock Research Station, Kattupakkam, Tamil Nadu, India. The skulls of the animals were opened to know the prevalence of Coenurus cyst in the brain. Out of 12.30 %, only 3.28 % sheep showed clinical signs while the remaining were apparently healthy (9.02 %). C. cerebralis cysts were observed in cerebrum, cerebellum and on spinal cord, averaging 66.67, 26.67 and 6.66 %, respectively. Among different age groups of sheep, highest infection rate was observed in rams (20.69 %) followed by ewes (10.00 %), young males (9.09 %) and young females (8.33 %). Males (17.50 %, 7/40) were more infected compared to the female sheep (9.76 %, 8/82). Grossly, ventral cerebrum was congested and depression in sulci was noticed. Posterior portion of the skull showed severe congestion and haemorrhage. Severe congestion was also noticed on the gyri of right cerebral hemisphere.

8.
Fish Shellfish Immunol ; 67: 368-381, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28606862

RESUMO

A pathobiological study was conducted using Vibrio parahaemolyticus (VP) strain isolated from vibriosis affected shrimp (Penaeus vannamei) farms in Kancheepuram and Thiruvallur districts of Tamil Nadu during August 2014 to February 2015. The isolate was identified based on the morphological, physiological, biochemical and molecular characters. LD50 value with intramuscular injection was determined as 2.6 × 104 cfu/shrimp and sequential pathology was studied giving 6.1 × 103 cfu/shrimp (LD25). Total plate count (TPC) and total Vibrio count (TVC) in water, pond sediment, haemolymph, muscle, HP and gut were found significantly (P < 0.01) higher in natural cases than the experimental set up. Clinical signs and lesions observed in the natural and experimental cases were anorexia, lethargy, cuticle softening, loose shells, abdominal muscle cramp, red discoloration, opaque and whitish abdominal and tail musculature, necrosis of exoskeleton or splinter burns, reddish pleural borders of antennae, uropods and telson, swollen tail fan, ulcers, moribund shrimp sinking to bottom, and mortalities with shrunken discoloured HP with empty gut. Total haemocyte count (THC), small nongranular haemocyte (SNGH), large nongranular haemocyte (LNGH), small granular haemocyte (SGH) and large granular haemocyte (LGH) counts lowered significantly (P < 0.01) at 3, 6, 12, 24, 48, 96 and 192 h post injection (p.i). No LGH were found after 96 h of challenge. The post injection qPCR analyses of haemocytes showed up-regulations of penaeidin-3a, lysozyme, prophenoloxidase I, prophenoloxidase II and serine protein at 3 and 6 h of infection. There was total down-regulation of crustin from 3 to 192 h p.i. There was a remarkable elevation in the level of proPO I with concomitant depletion of proPO II. The pattern of up- and down-regulations in proPO I and SP were similar. The post infection qPCR analyses showed that these immune related genes could be used as markers for assessing the immune status of P. vannamei. Major histopathological manifestations observed were haemocyte infiltration/nodule in the epidermis, skeletal and cardiac muscles, atrophy of the excretory organ, and disrupted HP tubules with diffuse interstitial edema and haemocytic infiltration. Further HP showed that there was thickening of intertubular space, karyomegaly with prominent nucleoli, rounding and sloughing of HP tubular epithelium, many mitotic figures with bacterial colonies and apoptotic bodies, separation of shrunken tubule epithelium from myoepithelial fibers, regeneration of tubules, cystic, dilated and vacuolated appearance of HP tubules, hypoplastic changes in the tubules with no B, R and F cells, granuloma formation, concretions in tubules, calcification, necrosis, and washed out appearance with complete loss of architecture. The progression of the degenerative changes in the HP tubular epithelial cells was from proximal to distal end. In haematopoietic organ, increased mitotic activities with focal to extensive depletion and degeneration were observed. Degeneration of the stromal matrix with spheroid formation in lymphoid organ was observed among the Vp infected natural and experimental animals. Degeneration of glandular structures in the prehensile appendages with bacterial colonies, melanization and loss of epithelial layer in oesophagus, swelling and loss of architecture with mucinous secretion in the stomach, degeneration of peritrophic membrane in the lumen of intestine were observed in field cases but not in the experimental studies. Further, this study established the pathobiology of the Vp isolate to P. vannamei.


Assuntos
Regulação da Expressão Gênica/imunologia , Hemócitos/imunologia , Imunidade Inata/genética , Penaeidae/imunologia , Penaeidae/microbiologia , Vibrio parahaemolyticus/fisiologia , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Índia
9.
Indian J Dermatol ; 62(2): 171-177, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28400637

RESUMO

BACKGROUND: Pemphigus is an acquired immunobullous disorder in which antibodies are directed against epidermal cadherins. Despite the commercial availability and less cost of enzyme-linked immunosorbent assays (ELISAs) to detect antidesmoglein 1 (Dsg1) and anti-Dsg3, immunofluorescence is still widely used for confirmation of diagnosis. AIMS: (1) To compare the usefulness of indirect immunofluorescence (IIF) and ELISA tests in the diagnosis of pemphigus. (2) To find the clinical correlation between the tests and severity of the disease. MATERIALS AND METHODS: Sixty-one patients (27 women and 34 men, age distribution from 20 to 75) were clinically diagnosed as pemphigus (pemphigus foliaceus - 11, pemphigus vulgaris - 50) and were recruited for the study. IIF and Dsg ELISA were performed and the findings were compared with each other and with the pemphigus area activity score. Data were entered in SPSS and were analyzed using Kruskal-Wallis test. RESULTS: There was a moderate positive correlation between the cutaneous score and Dsg1 titer, and mucosal score and Dsg3 titer. The titer of IIF showed statistically significant positive correlation with the cutaneous score but not the mucosal score. Dsg ELISA showed higher sensitivity (90.2%) than IIF (75.4%) in the diagnosis of pemphigus. CONCLUSIONS: Dsg ELISA is a more sensitive method than IIF and shows more correlation with the disease severity.

10.
Vet Parasitol Reg Stud Reports ; 10: 35-38, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-31014595

RESUMO

We report the detailed gross, histopathological and immunohistochemical study of Strobilocercus fasciolaris infection, the metacestodal stage of Taenia taeniaeformis, in the liver of laboratory Wistar rats. Necropsy examination of seventeen rats revealed transparent or white or cream to clear, thick walled cysts, 1 to 97 in number, measuring about 2mm to 12mm on one or many of the liver lobes and containing strobilocercus of Taenia taeniaeformis. Histopathological examination revealed the presence of the cross-section of larva surrounded by a thick fibrous capsule and moderate infiltration of lymphocytes, plasma cells and a few eosinophils. Fatty degeneration of hepatocytes, gastric mucosal hyperplasia, distended gastric glands and marked increase in the mucosal epithelial cells and goblet cells in the duodenum were also observed. Contamination of feed and bedding materials seems to be the probable source in these naturally infected rats.


Assuntos
Ciência dos Animais de Laboratório , Hepatopatias/veterinária , Doenças dos Roedores/parasitologia , Taenia/classificação , Teníase/veterinária , Animais , Duodeno/patologia , Fibrossarcoma/parasitologia , Fibrossarcoma/patologia , Fibrossarcoma/veterinária , Imuno-Histoquímica , Índia/epidemiologia , Fígado/parasitologia , Fígado/patologia , Hepatopatias/parasitologia , Hepatopatias/patologia , Neoplasias Hepáticas/parasitologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/veterinária , Ratos , Ratos Wistar , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/patologia , Teníase/epidemiologia , Teníase/parasitologia , Teníase/patologia
12.
Indian J Dermatol ; 61(3): 329-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27293257

RESUMO

Epidermolysis bullosa acquisita (EBA) is an acquired subepidermal bullous disorder characterized by autoantibodies against Type VII collagen. It usually affects adults; childhood EBA is rare. We describe a 10-year-old girl presenting with recurrent tense blisters predominantly on legs, dorsa of hands and feet accompanied by oral erosions since the age of 5 years. Direct immunofluorescence (IF) microscopy showed linear deposition of IgG and C3 along the basement membrane zone (BMZ); indirect IF microscopy on salt-split skin revealed staining of IgG to the dermal side of the split. The patient's serum did not show BMZ staining in recessive dystrophic epidermolysis bullosa skin deficient for Type VII collagen, thus confirming autoantibody reactivity against Type VII collagen. Circulating antibodies against the immunodominant noncollagenous 1 domain of Type VII collagen were detected by ELISA and immunoblotting studies. The patient was treated with oral corticosteroids and dapsone with good improvement.

13.
Chem Biol Interact ; 249: 23-35, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26915975

RESUMO

The present study investigated the anticancer activity of 2,3-dihydroxy-9,10-anthraquinone against different cancer cells such as MCF-7, COLO320, HepG-2, Skov-3, MOLM-14, NB-4, CEM, K562, Jurkat, HL-60, U937, IM-9 and Vero. 2,3-dihydroxy-9,10-anthraquinone showed good antiproliferative activity against COLO320 cells when compared to other tested cells. The cytotoxicity results showed 79.8% activity at the dose of 2.07 µM with IC50 value of 0.13 µM at 24 h in COLO320 cells. So we chose COLO320 cells for further anticancer studies. mRNA expression was confirmed by qPCR analysis using SYBR green method. Treatment with 2,3-dihydroxy-9,10-anthraquinone was found to trigger intrinsic apoptotic pathway as indicated by down regulation of Bcl-2, Bcl-xl; up regulation of Bim, Bax, Bad; release of cytochrome c and pro-caspases cleaving to caspases. Furthermore, 2,3-dihydroxy-9,10-anthraquinone stopped at G0/G1 phase with modulation in protein levels of cyclins. On the other hand PI3K/AKT signaling plays an important role in cell metabolism. We found that 2,3-dihydroxy-9,10-anthraquinone inhibits PI3K/AKT activity after treatment. Also, COX-2 enzyme plays a major role in colorectal cancer. Our results showed that the treatment significantly reduced COX-2 enzyme in COLO320 cells. These results indicated antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone involving apoptotic pathways, mitochondrial functions, cell cycle checkpoint and controlling the over expression genes during the colorectal cancer. Molecular docking studies showed that the compound bound stably to the active sites of Bcl-2, COX-2, PI3K and AKT. This is the first report of anticancer mechanism involving 2,3-dihydroxy-9,10-anthraquinone in COLO320 cells. The present results might provide helpful suggestions for the design of antitumor drugs toward colorectal cancer treatment.


Assuntos
Antraquinonas/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocromos c/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores de Ciclo-Oxigenase 2/farmacologia , Fase G1/efeitos dos fármacos , Células HL-60 , Células Hep G2 , Humanos , Células K562 , Células MCF-7 , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Simulação de Acoplamento Molecular/métodos , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células U937
14.
Chem Biol Interact ; 242: 81-90, 2015 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-26415618

RESUMO

The present study was undertaken to investigate the anticancer activity of methyl caffeate isolated from Solanum torvum Swartz. fruit and to explore the molecular mechanisms of action in MCF-7 cells. Cytotoxic properties of hexane, ethyl acetate and methanol extracts were carried out against MCF-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Ethyl acetate extract showed good cytototoxic activities compared to hexane and methanol extracts. Methyl caffeate was isolated from the ethyl acetate extract using column chromatography. Cytotoxic properties of methyl caffeate was investigated against MCF-7, A549, COLO320, HepG-2 and Vero cells. The compound showed potent cytotoxic properties against MCF-7 cells compared to A549, COLO320 and HepG-2 cells. Methyl caffeate significantly reduced cell proliferation and increased formation of fragmented DNA and apoptotic body in MCF-7 cells. Bcl-2, Bax, Bid, p53, caspase-3, PARP and cytochrome c release were detected by western blot analysis. The activities of caspases-3 and PARP gradually increased after the addition of isolated compound. Bcl-2 protein was down regulated; Bid and Bax were up regulated after the treatment with methyl caffeate. Molecular docking studies showed that the compound bound stably to the active sites of poly (ADP-ribose) polymerase-1 (PARP1), B cell CLL/lymphoma-2 (BCL-2), E3 ubiquitin-protein ligase (MDM2) and tubulin. The results strongly suggested that methyl caffeate induced apoptosis in MCF-7 cells via caspase activation through cytochrome c release from mitochondria.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Solanum/química , Animais , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Caspases/metabolismo , Chlorocebus aethiops , Citocromos c/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Frutas/química , Células Hep G2/efeitos dos fármacos , Humanos , Células MCF-7/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Simulação de Acoplamento Molecular , Células Vero/efeitos dos fármacos
15.
Bioorg Med Chem Lett ; 25(19): 4232-8, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26296475

RESUMO

Antimicrobial agents 4a-g and 5a-g with very good potency were synthesized with 100% ee from phenylpropanolamine (norephedrine) by BF3 catalyzed three components one pot Mannich reaction in good yields. Obtained compounds were characterized using spectral techniques. Antimicrobial study of these compounds revealed a good to very high potential activity against tested microbes when compared to standard antimicrobial drugs streptomycin and ketoconazole. These synthesized compounds exhibited significant minimum inhibitory concentration (MIC) values against Gram positive and Gram negative bacteria. Amongst compound 4b, 4c, 4d, 4e, 5a, and 5e exhibited very high potent MIC values against tested twelve bacteria and three fungi when compared to control. When subjected to molecular docking, in silico studies revealed significant binding energies ranging from -7.06 to -8.90 kcal/mol for all obtained compounds towards target receptor DNA topoisomerase IV and amongst compounds 4b and 4d have shown maximum binding energies 8.70 and 8.90 kcal/mol, respectively.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Bases de Mannich/química , Bases de Mannich/farmacologia , Simulação de Acoplamento Molecular , Fenilpropanolamina/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Boranos , Catálise , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenilpropanolamina/síntese química , Fenilpropanolamina/química , Relação Estrutura-Atividade
16.
Bioorg Med Chem Lett ; 25(14): 2753-7, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26028159

RESUMO

A novel series of thiophene and benzodioxole appended thiazolyl-pyrazoline derivatives have been designed, synthesized and evaluated against different bacteria and fungi. The antimicrobial activity of the synthesized compounds were screened using MIC method and were proved synthesized compounds 7o, 7r and 7t to show good antimicrobial activity against bacteria and fungi. In silico molecular docking studies revealed that all the synthesized molecules showed good binding energy toward the target receptor DNA topoisomerase IV, ranging from -10.42 to -11.66 kcal/mol.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Micro-Ondas , Pirazóis/química , Tiazóis/química , Anti-Infecciosos/química , Benzodioxóis/química , Sítios de Ligação , DNA Topoisomerase IV/antagonistas & inibidores , DNA Topoisomerase IV/metabolismo , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica , Tiofenos/química
17.
Biomed Res Int ; 2015: 727304, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25632399

RESUMO

Adhatoda vasica (L.) (Acanthaceae) is used in the indigenous system of medicine in India. The alkaloid Vasicine was isolated from ethanolic extract of the leaves of A. vasica using column chromatography. Vasicine acetate was obtained by acetylation of Vasicine. Vasicine acetate exhibited good zone of inhibition against bacteria: 10 mm against E. aerogenes, 10 mm against S. epidermidis, and 10 mm against P. aeruginosa. Vasicine acetate showed minimum inhibitory concentration values against bacteria: M. luteus (125 µg/mL), E. aerogenes (125 µg/mL), S. epidermidis (125 µg/mL), and P. aeruginosa (125 µg/mL). The radical scavenging activity of Vasicine acetate was the maximum at 1000 µg/mL (66.15%). The compound showed prominent cytotoxic activity in vitro against A549 lung adenocarcinoma cancer cell line. Quantification of Vasicine and Vasicine acetate by HPLC-DAD analysis showed their contents to be 0.2293% and 0.0156%, respectively, on dry weight basis of the leaves. Vasicine acetate could be probed further in drug discovery programme.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Justicia/química , Quinazolinas/química , Quinazolinas/isolamento & purificação , Quinazolinas/farmacologia , Alcaloides/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Testes de Sensibilidade Microbiana , Picratos/química , Extratos Vegetais/farmacologia , Espectrofotometria Ultravioleta
18.
Bioorg Med Chem Lett ; 25(2): 389-99, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25435149

RESUMO

In the present study, a series of novel highly functionalized spiropyrrolidine-oxindoles have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide formed from isatin and various amino acids such as sarcosine, proline and thioproline with the dipolarophile (E)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-(1H-indole-3-carbonyl)acrylonitrile under optimized conditions. All the synthesized compounds were evaluated for their antimicrobial activity and shown significant activity.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Indóis/química , Pirrolidinas/química , Compostos de Espiro/síntese química , Compostos de Espiro/farmacologia , Células Cultivadas , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxindóis , Estereoisomerismo , Relação Estrutura-Atividade
19.
Indian J Exp Biol ; 53(12): 779-85, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26742322

RESUMO

Leptospirosis is a bacterial disease caused by bacteria of the genus Leptospira affecting humans and animals. Untreated leptospirosis may result in severe kidney damage, meningitis, liver failure, respiratory distress, and even death. Virulent leptospirosis can rapidly enter kidney fibroblasts and induce a programmed cell death. Thus, it is a challenge for immunologists to develop an effective and safe leptospirosis vaccine. Here, we compared the commercial canine leptospira vaccine and recombinant proteins (OmpL1 and LipL41) with and without adjuvant in terms of immune response and challenge studies in hamsters and immune response studies alone in experimental dogs. The outer membrane proteins viz., lipL41 and OmpL1 of leptospira interrogans serovars icterohaemorrhagiae were amplified. The primers were designed in such a way that amplified products of OmpL1 and lipL41 were ligated and cloned simultaneously into a single vector. The cloned products were expressed in E. coli BL21 cells. The immunoprotection studies were conducted for both recombinant proteins and commercial vaccine. The challenge experiment studies revealed that combination of both rLip41 and rOmpL1 and commercial vaccine gave 83% and 87% protection, respectively. Histopathological investigation revealed mild sub lethal changes were noticed in liver and kidney in commercially vaccinated group alone. The immune responses against recombinant leptospiral proteins were also demonstrated in dogs.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Leptospira/imunologia , Leptospirose/prevenção & controle , Vacinas Sintéticas/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Vacinas Bacterianas/genética , Cricetinae , Modelos Animais de Doenças , Cães , Imunização , Leptospira/genética , Leptospirose/imunologia , Leptospirose/microbiologia , Vacinas Sintéticas/genética
20.
Indian Dermatol Online J ; 5(Suppl 1): S33-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25506561

RESUMO

Rowell syndrome is a rare disease consisting of erythema multiforme-like lesions associated with lupus erythematosus. The syndrome occurs mostly in middle-aged women. The authors describe the syndrome in a 15-year-old boy who responded well to systemic steroids and hydroxychloroquine.

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