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A series of 1,2,4-triazolo-quinazolinones and 1,2-benzisothiazolone derivatives (S1-S12) were successfully synthesized as environmentally friendly alternatives to copper-based antifouling paints using N-alkylation, cyclocondensation, and one-pot three-component and amide coupling reactions. The monoclinic structure of single-crystal 1,2,4-triazolo-quinazolin-acetic acid (S8) was confirmed by single-crystal X-ray diffraction analysis. All the synthesized molecules were studied for their in silico molecular docking interactions with three target proteins, namely, RbmA, ToxR, and Bap. Following that, the antialgal activity was assessed against two types of marine algae: Chlorella sp. and Chaetoceros curvisetus. The minimal inhibitory concentration and zone of inhibition have been used to evaluate the antibacterial activities of S1-S12 against both marine Gram-positive (Staphylococcus aureus) and Gram-negative (Vibrio parahemolyticus and Vibrio vulnificus) bacteria. Additionally, antifouling studies have been done on all the compounds, and among them, 1,2,4-triazolo-quinazolinyl-acetate (S7), 1,2,4-triazolo-quinazolinyl-acetic acid (S8), 1,2,4-triazolo-quinazolinyl-oxobutanoate (S9), benzo[d]isothiazolyl butanoate (S10), benzo[d]isothiazolyl-acetic acid (S11), and 1,2,4-triazolo-quinazolinyl-acetyl-benzo[d]isothiazolone (S12) exhibited good antialgal, antibacterial, and antifouling activities.
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Billions of people are affected by fungal infection worldwide, which is a major cause of morbidity and mortality in humans. Regardless of development in the field of antifungal therapeutics over the last three decades, multidrug resistance and limited efficacy of available antifungal drugs are very prominent and still a great hurdle in the patient treatment. The current antifungal pipeline is dry, which is needed to be strengthened. Although several strategies have been implemented over time to discover novel promising antifungal leads, but very little emphasis has been given to address the gap of fungal target identification. Undeniably, the need for identifying novel cellular fungal targets is as vital as discovering novel antifungal leads and a structural bioinformatics approach could be an effective strategy in this regard. To address the issue, we have performed in silico screening to identify a few potent multiple targeting ligands and their respective antifungal targets. Thus, we offer a perspective on the phenomena of 'target shortage' and least explored 'multiple targeting' being the most underrated challenges in antifungal drug discovery. 'Structural bioinformatics' could be an effective approach in the recognition of new/innovative antifungal target and identification/development of novel antifungal lead molecule aiming multiple molecular targets of the fungal pathogen.
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Antifúngicos , Biologia Computacional , Desenvolvimento de Medicamentos , Descoberta de Drogas , Micoses/tratamento farmacológico , Antifúngicos/química , Antifúngicos/uso terapêutico , Fungos/crescimento & desenvolvimento , HumanosRESUMO
Underestimating fungal infections led to a gap in the development of antifungal medication. However, rising rates of morbidity and mortality with fungal infection have revealed an alarming rise in antifungal resistance also. Due to the eukaryotic properties of fungi and the close evolutionary similarity between fungal cells and human hosts, therapeutic targeting of Candida infections is troublesome, along with the development of resistance. The discovery of new antifungals is so far behind schedule that the antifungal pipeline is nearly empty. Previously, we have reported the activity and susceptibility of Sodium lignosulfonate (LIG) against C. albicans. In this work, we have established the mechanistic actions of LIG's activity. We performed flow cytometric analysis for membrane integrity, ergosterol binding assay, crystal violet assay, and membrane leakage assay to analyze quantitatively that the C. albicans membrane is being disrupted in response to LIG. Electron microscopic analysis with SEM and TEM confirmed changes in Candida cellular morphology and membrane perturbation respectively. These findings indicated that LIG causes cell membrane damage in C. albicans. This knowledge about LIG's mechanism of action against C. albicans could be used to explore it further as a lead antifungal molecule to develop it as a potent candidate for antifungal therapeutics in the future.
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Antifúngicos , Candida albicans , Lignina , Lignina/análogos & derivados , Candida albicans/citologia , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacosRESUMO
Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.
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Tratamento Farmacológico da COVID-19 , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Cuidados para Prolongar a Vida , Idoso , COVID-19/complicações , COVID-19/mortalidade , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Respiração Artificial , Choque Séptico/etiologia , Método Simples-CegoRESUMO
Regardless of considerable progress in synthetic plastic or polymer-based industry, its low biodegradability is a critical issue. Nevertheless, natural "biopolymers" are gradually replacing them for being inherently biodegradable, eco-friendly with other unique properties. This article aims to present a review regarding different extraction techniques of biopolymers [natural (cellulose, chitin, lignin, pectin, starch, xylan), synthetic (polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polyvinyl alcohol (PVA), polymethayl methacrylate (PMMA)] from waste using bio-based methods. The role of bio-based techniques in terms of conventional/ecologically stable strategies for biomass pre-treatment was investigated for proper utilization of waste. The review summarizes strong interplay between technological and future challenges of biopolymer extraction from waste and paints a discussion of how conventional resources could be replaced with more environmentally friendly materials. Therefore, we advocate the implementation of biomass waste from food, organic, and other bio-based industries that revolutionizes the stance of biopolymer in various emerging fields.
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Biomassa , Biopolímeros/química , Biotecnologia/métodos , Celulose/química , Animais , Biodegradação Ambiental , Adesão Celular , Quitina/química , Humanos , Plásticos , Poliésteres/química , Poli-Hidroxialcanoatos/química , Eliminação de Resíduos , Solventes/química , Açúcares/químicaRESUMO
The present investigation demonstrates the longevity-promoting effects of 3-methyl-3-buten-1-ol (isoprenol) in the animal model Caenorhabditis elegans that might be served as a lead nutraceutical in geriatric research. Our results showed that 0.5 mM isoprenol extended the mean lifespan of worms by 25% in comparison to control worms. Isoprenol also significantly enhanced survival of the worms under various stress conditions. It was found that the longevity-promoting effects of isoprenol were associated with improved age-associated physiological behaviour and reduced intracellular reactive oxygen species (ROS) accumulation. Finally, studies with gene-specific mutants revealed the involvement of pro-longevity transcription factors (TFs) DAF-16 and SKN-1 with simultaneous over-expression of GST-4 and SOD-3 in isoprenol treated worms. In silico analysis revealed the binding affinity of isoprenol with DAF-16 and SKN-1 TFs. Together, the findings suggest that isoprenol is able to enhance the lifespan of C. elegans and embarks its potential in the developments of formulations for age-related ailments.
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Butanóis/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/crescimento & desenvolvimento , Longevidade/efeitos dos fármacos , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Modelos Animais , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/metabolismoRESUMO
Salmonella typhimurium is the causative agent of severe human infections and mortality throughout the world. Pacing advent of new resistance mechanisms in this microorganism exists, rendering treatment of infectious disease difficult. Ciprofloxacin is no longer considered the first choice of antimicrobial agent due to the emergence of resistance. Therefore, the need for scenario is to find out novel drug target and its potential inhibitor to fight against this pathogen. The present study was undertaken to find out a novel drug target and its inhibitor for improving the current therapeutic methods for treating Salmonella infections. It is found that l-asparaginase is exploited by the pathogen for its survival benefit. Therefore, it could be targeted to fight against lethality caused by Salmonella infections. In the present in silico study, the 3-D structure of the enzyme l-asparaginase was modelled by using homology modeling technique. Thereafter, molecular docking studies and ADMET prediction to assess pharmacokinetic profiles of test ligands (eugenol and its derivative) was performed. The results show that eugenol and its derivative are capable of inhibiting the Salmonella virulent protein l-asparaginase. There were 18 ligands including ciprofloxacin (used as reference) were docked. The lowest binding energy was observed with eugenol derivative 8 i.e -5.836 kcal/mol while for ciprofloxacin was -4.661 kcal/mol. The docking of the eugenol derivative 8 with l-asparaginase revealed a strong interaction between them with two hydrogen bonds. Thr 35 and Asp 116 residues are actively participating in this interaction. The result of ADMET profiling suggests the potency of eugenol and its derivatives against Salmonellal-asparaginase-II as a compelling drug candidate. These findings provide useful information on the biological role, structure-based drug design and potent inhibitor of l-asparaginase for the development of effective therapeutic molecule against Salmonella infection.
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Asparaginase/efeitos dos fármacos , Eugenol/antagonistas & inibidores , Eugenol/química , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/enzimologia , Asparaginase/química , Sítios de Ligação , Ciprofloxacina/química , Desenho de Fármacos , Eugenol/farmacocinética , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação Proteica , Infecções por Salmonella/tratamento farmacológico , Salmonella typhimurium/patogenicidade , Fatores de VirulênciaRESUMO
With increasing global cases and mortality rates due to COVID-19 infection, finding effective therapeutic interventions has become a top priority. Marine resources are not explored much and to be taken into consideration for exploring antiviral potential. Chitosan (carbohydrate polymer) is one such bioactive glycan found ubiquitously in marine organisms. The presence of reactive amine/hydroxyl groups, with low toxicity/allergenicity, compels us to explore it against SARS-CoV-2. We have screened a library of chitosan derivatives by site-specific docking at not only spike protein Receptor Binding Domain (RBD) of wild type SARS-CoV-2 but also on RBD of B.1.1.7 (UK) and P.1 (Brazil) SARS-CoV-2 variants. The obtained result was very interesting and ranks N-benzyl-O-acetyl-chitosan, Imino-chitosan, Sulfated-chitosan oligosaccharides derivatives as a potent antiviral candidate due to its high binding affinity of the ligands (-6.0 to -6.6 kcal/mol) with SARS-CoV-2 spike protein RBD and they critically interacting with amino acid residues Tyr 449, Asn 501, Tyr 501, Gln 493, Gln 498 and some other site-specific residues associated with higher transmissibility and severe infection. Further ADMET analysis was done and found significant for exploration of the future therapeutic potential of these three ligands. The obtained results are highly encouraging in support for consideration and exploration in further clinical studies of these chitosan derivatives as anti-SARS-CoV-2 therapeutics.
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Antivirais/farmacologia , Quitosana/farmacologia , Variação Genética , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Antivirais/química , Sítios de Ligação , Brasil , Quitosana/química , Modelos Moleculares , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Reino Unido , Internalização do Vírus/efeitos dos fármacosRESUMO
Terpenes and their derivatives have been used conventionally as potential dietary supplements to boost the nutritional value of endless food products. Several plant-based complex terpenoid and their derivatives have been reported for a wide range of medicinal and nutritional properties. However, their simple counterparts, whose production is relatively easy, sustainable, and economic from food-grade microbial sources, have not been studied yet for any such biological activities. The present study aimed to investigate the longevity-promoting property and neuromodulatory effects of 3,3-dimethylallyl alcohol (Prenol), one of the simplest forms of terpenoid and a constituent of fruit aroma, in the animal model Caenorhabditis elegans. Prenol supplementation (0.25 mM) augmented the lifespan of wild-type nematodes by 22.8% over the non-treated worms. Moreover, a suspended amyloid-ß induced paralysis and reduced α-synuclein aggregation were observed in Prenol-treated worms. The lifespan extending properties of Prenol were correlated with ameliorated physiological parameters and increased stress (heat and oxidative) tolerance in C. elegans. In silico and gene-specific mutant studies showed that pro-longevity transcription factors DAF-16, HSF-1, and SKN-1 were involved in the improved lifespan and health-span of Prenol-treated worms. Transgenic green fluorescent protein-reporter gene expression analysis and relative mRNA quantification (using real-time PCR) demonstrated an increase in the expression of DAF-16, HSF-1, and SKN-1 transcription factors and their downstream target genes in Prenol-treated worms. Together, the findings suggest that small molecules, like Prenol, could be explored as a potential alternate to develop therapeutics against aging and age-related ailments.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Hemiterpenos , Longevidade , Neuroproteção , Estresse Oxidativo , Espécies Reativas de OxigênioRESUMO
Chronic kidney disease (CKD) not associated with known risk factors has been reported from parts of India and is presumed to be similar to CKD of unknown etiology (CKDu) that has been described from Central America. The reports from India have been fragmented without clear description of the disease phenotype or its determinants. This paper summarizes the current state of knowledge around CKDu in India based on a review of literature, multi-stakeholder consultation, and a survey of Indian nephrologists. We also contacted individual research groups to solicit data. Our findings suggest that that CKDu is reported from most regions in India; however, it is interpreted differently from the phenotype described from Central America and Sri Lanka. The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. Well-designed prospective field studies with appropriate diagnostic workup are needed to establish the disease burden and identify etiologies, along with socioeconomic and health consequences, the intersection with the environment, and the public health response. Community-based research should phenotype the entire CKD population rather than be restricted to cases with presumed CKDu based on predefined criteria. Guidelines are needed for clinical evaluation, referral, management, and harmonization of clinical documentation and health records. More data are needed to support the existence of a unique CKDu phenotype in India.
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Candida albicans is a prominent human fungal pathogen. Current treatments are suffering a massive gap due to emerging resistance against available antifungals. Therefore, there is an ardent need for novel antifungal candidates that essentially have more than one target, as most antifungal repertoires are single-target drugs. Exploration of multiple-drug targeting in antifungal therapeutics is still pending. An extensive literature survey was performed to categorize and comprehend relevant studies and the current therapeutic scenario that led researchers to preferentially consider multitarget drug-based Candida infection therapy. With this article, we identified and compiled a few potent antifungal compounds that are directed toward multiple virulent targets in C. albicans. Such compound(s) provide an optimistic platform of multiple targeting and could leave a substantial impact on the development of effective antifungals.
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Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Descoberta de Drogas , Farmacorresistência Fúngica/efeitos dos fármacosRESUMO
Visceral leishmaniasis (VL) is one of the most devastating diseases of the tropical region caused by protozoan parasite Leishmania donovani. So far, there is no effective drug and vaccine available against this fatal disease. The DEAD-box RNA helicase is quite essential for the RNA processing, amastigote differentiation and infectivity in Leishmania. In this study, L. donovani DEAD-box RNA helicase (LdHel-67) was evaluated as a potential drug target against VL. Using in-silico approach we have identified ligands that can specifically bind to this protein by using various application of Schrodinger (Maestro, version 10.5, LLC, NY 2016-1). We have shortlisted 10 ligands with positive interaction against the selected target based on their in-silico activity and identified three potential compounds viz. carvacrol, vanillin, and the p-coumaric acid having a maximum affinity for this LdHel-67 protein. After vigorous in-silico analysis, these ligands were tested in-vitro against L. donovani. These ligands were safer on the J774A.1 macrophages and were effective against promastigotes and disease-causing intracellular amastigotes. This is the first report of antileishmanial potential of carvacrol, vanillin and p-coumaric acid targeting LdHel-67. Thus, the present study will help in the search for target specific inhibitors to facilitate the development of new drugs against VL.
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Antiprotozoários/farmacologia , RNA Helicases DEAD-box/metabolismo , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/enzimologia , Sequência de Aminoácidos , Linhagem Celular , RNA Helicases DEAD-box/química , Avaliação Pré-Clínica de Medicamentos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/microbiologia , Simulação de Acoplamento Molecular , Conformação ProteicaRESUMO
The essential oil (EO) composition of the aerial parts of Erigeron multiradiatus (Lindl.ex DC.) Benth growing wild in the central Himalayan region of Uttarakhand, India, was analyzed by capillary gas chromatography with a flame ionization detector and gas chromatography-mass spectrometry. A sum of 12 constituents was identified, representing 97.81% of the oil composition. The oil was composed mainly of oxygenated monoterpenes (88.95%), sesquiterpene hydrocarbons (5.61%), oxygenated sesquiterpenes (3.05%), and monoterpene hydrocarbons (0.20%). Major constituents identified were trans-2-cis-8-matricaria-ester (77.79%), cis-lachnophyllum ester (11.04%), zingiberene (4.43%), and spathulenol (1.59%). Further, the leishmanicidal effect of EO and the purified compound trans-2-cis-8-matricaria-ester has been investigated against Leishmania donovani promastigotes and intracellular amastigotes. EO and trans-2-cis-8-matricaria-ester were safer for the hamster peritoneal macrophage and lethal to promastigotes and intracellular amastigotes at different concentrations. Further, using an in silico approach, these four compounds were tested against 10 major proteins of L. donovani associated with its virulence. Out of them, only trans-2-cis-8-matricaria-ester was found to be effective against the four target proteins, namely, l-asparaginase-1-like protein, metacaspase 2, metacaspase 1, and DNA topoisomerase II of L. donovani. The results indicate that EO contains trans-2-cis-8-matricaria-ester as a major component and showed antileishmanial activity which may facilitate discovery of new lead molecules for developing herbal medicines against visceral leishmaniasis.
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In spite of therapeutic development against life threatening fungal pathogens like Candida albicans, the repertoire of effective antifungal drugs is lagging. The emergence and persistence of azole/echinocandin resistance and other cases of multi-drug resistance have led to the failure of the antifungal treatment regime. This troublesome scenario has steered a need for the development of novel leads. Computer aided in-silico drug design using virtual screening, molecular docking, drug likeness, absorption, distribution, metabolism, excretion, and toxicity analysis for the identification of lead compounds for further in-vitro analysis is a cost effective and time-saving strategy. The present study used these strategies to discover novel lead antifungal from the pool of second largest occurring natural compound lignin. After the virtual screening of lignin derivatives, Sodium lignosulfonate (LIG) was identified as the best lead for further analysis. After this vigorous in-silico analysis, LIG was then tested in-vitro against 5 different Candida species. MIC value of LIG against Candida spp. was found to be 64-128µg/ml. The study is revealing LIG as a potent and persuasive antifungal agent. In the race of Candida therapeutics, the revelation of the antifungal potential of such natural compounds might impact and diversify the discovery and development of novel antifungal agent.
Assuntos
Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Lignina/análogos & derivados , Antifúngicos/farmacologia , Candida albicans/patogenicidade , Candidíase/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Humanos , Lignina/química , Lignina/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento MolecularRESUMO
The effective long-term cryopreservation of human mesenchymal stem cells (MSCs) is an essential prerequisite step and represents a critical approach for their sustained supply in basic research, regenerative medicine, and tissue engineering applications. Therefore, attempts have been made in the present investigation to formulate a freezing solution consisting of a combination of Selaginella bryopteris water-soluble extract with and without dimethyl sulfoxide (Me2SO) for the efficient long-term storage of human umbilical cord blood- (hUCB-) derived MSCs. The cryopreservation experiment using the formulated freezing solution was further performed with hUCB MSCs in a controlled rate freezer. A significant increase in postthaw cell viability and cell attachment of MSCs was achieved with freezing medium containing Selaginella bryopteris water extract along with 10% Me2SO as compared to the freezing medium containing Me2SO (10% v/v) alone. Furthermore, the decreasing apoptotic events and reactive oxygen species production along with increasing expression of heat shock proteins also confirmed the beneficial effect of Selaginella bryopteris water extract. The beneficial effect of Selaginella bryopteris water extract was validated by its ability to render postpreservation high cell viability. In conclusion, the formulated freezing solution has been demonstrated to be effective for the standardization of cryopreservation protocol for hMSCs.
Assuntos
Apoptose/efeitos dos fármacos , Criopreservação/métodos , Extratos Vegetais/farmacologia , Selaginellaceae/química , Citoesqueleto de Actina/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dimetil Sulfóxido/química , Sangue Fetal/citologia , Congelamento , Proteínas de Choque Térmico/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Selaginellaceae/metabolismo , Água/químicaRESUMO
Candidiasis caused by primarily Candida albicans poses serious threat due to dry pipeline and ineffective antifungal strategy against resistance. In this study we propose to target genes involved in efflux mediated Multi drug resistance. The main objective of this study was to understand the regulatory interactions responsible for activating a major MFS transporter gene of Candida albicans. Another aim was to identify the docking effect of certain antifungal compounds upon the transcription factor effectively controlling FLU1. The in silico study carried out here aims at control of gene expression at initial levels. This approach helps to understand regulatory control of FLU1 based on which a predictive map was generated. This data focused on factors with major control that could be suitable target for antifungal agents. The docking results confirm the agreeable effect on the target transcription factor. Broadly this sort of study would account for understanding and targeting any significant gene which in turn would help in adjusting therapeutics accordingly. Further in silico ADMET analysis reported positive values that are indicative of a good antifungal compound with respect to pharmacokinetics. These tests are essential in assessment of good drug candidates because they not only help in refining better drug candidates but weeding out the unsuitable ones too.