Parisa Azerang

Synthesis and biological evaluation of coumarin derivatives as inhibitors of Mycobacterium bovis (BCG).

The coumarin compounds are an important class of biologically active molecules, which have attractive caught the attention of many organic and medicinal chemists, due to potential pharmaceutical implications and industrial applications. We herein report the one‐pot procedure for the efficient synthesis of coumarin derivatives using commercially available substrates via isocyanide‐based multicomponent condensation reactions. These compounds were evaluated for anti‐mycobacterium activity against Mycobacterium bovis (Bacillus Calmette–Guerin). The preliminary results indicated that all of the tested compounds showed relatively good activity against the test organism. The compounds 7e, 7l, and 7m showed high anti‐tuberculosis activity.

Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents.

BackgroundThe emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest.MethodsThis study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides.ResultsAll the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity.ConclusionsInhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.

Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes.

A series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. The derivatives were prepared by a sequential synthetic strategy including substitution at N‐1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. The derivatives were tested for their antimycobacterial activity against Mycobacterium bovis BCG, and the results revealed that among the synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t exhibited the highest activity with IC50 value of 3.91 μg/mL. The results indicate that the thiadiazole moiety plays a vital role in exerting antimycobacterial activity.

Design, Synthesis and Evaluation of New Azoles as Antifungal Agents: a Molecular Hybridization Approach

Two benzimidazole derivatives and one nitroimidazole derivative were designed using molecular hybridization approach. The designed compounds were synthesized and their in vitro antifungal activities were tested against Candida albicans and Saccharomyces cerevisiae strains. Based on the antifungal activity data, compound 9 containing 2-methyl-5-nitroimidazole moiety proved to be the most potent compound. It was more active than the reference drugs fluconazole and ketoconazole against S. cerevisiae.

Antimycobacterial evaluation of novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives synthesized by microwave-mediated Michael addition

The focus of this study is the synthesis and biological activity evaluation of a series of dibenzalaceton derivatives (3a-3n) and novel [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives (5a-5g) against Mycobacterium bovis, Bacillus Calmette-Guerin (BCG). Dibenzalacetone derivatives were synthesized by benzaldehyde derivatives. The [4,5-dihydro-1H-pyrazole-1-carbonyl]pyridine derivatives were synthesized by Michael addition reaction and using green chemistry microwave-mediated method. All compounds were evaluated against BCG and the activity expressed as minimum inhibitory concentration (MIC) in μM. The result showed good activity for all the compounds especially compounds (3a), (3n), and (5a) illustrated high activity (7.03, 8.10 and 5.37 μM, respectively).

Design and Antimicrobial Evaluation of 1-Methylimidazole Derivatives as New Antifungal and Antibacterial Agents

Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). In this research, a group of 1-methylimidazole derivatives were synthesized for evaluation as antibacterial and antifungal agents. Antimicrobial evaluation revealed that some of these compounds exhibited significant antimicrobial activities against tested pathogenic fungi and bacteria, wherein compounds 3 and 8 were most potent. To find the action mechanism, all of these compounds were subjected to docking studies using the AutoDock 4.2 program. The results show that all of the azoles (2 – 5, 7, and 8) interacted with 14α-DM, wherein azole – heme coordination, hydrogen binding, and -cation interactions were involved in the drug – receptor interaction. These studies offer some useful references in order to understand the action mechanism; moreover, performing the molecular design or modification of this series as a lead compound can assist in identifying new and potent antimicrobial agents.

Isolation of membrane-active fraction of Streptomyces spp. from soil

Purpose: To isolate and characterize the membrane-active antimicrobial fraction and isolate metabolite produced by Streptomyces in soil samples from Iran Methods : More than 60 Actinomycete strains were isolated from soil samples in Iran. A total number of 16 strains were studied using antimicrobial assay against Escherichia coli, Candida albicans and Staphylococcus aureus. Among these, three strains produced membrane-active metabolites based on artificial vesicle assay. Extracts of Streptomyces culture were obtained using ethyl acetate fractionation. Antimicrobial activity was evaluated by broth microdilution assay. Among these active extracts, one metabolite was isolated. Further fractionation and purification strategies were applied to finally identify the isolated metabolite using appropriate spectroscopic methods including thin layer chromatography (TLC), preparative thin-layer chromatography (PTLC), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and liquid chromatography–mass spectrometry (LC-MS). Results : Three strains isolated from the soil samples, namely, strains 0811, 08346 and 08317 showed the highest antifungal and antimicrobial activity in Tryptic Soy Broth (TSB) and International Streptomyces Projects 2 (ISP2) medium in the range of 46.8 to 62.5 μg/ml. Strain 08346 was selected for further chemical profiling based on TLC pattern and membrane activity. It yielded a purified compound which was determined to be a novel aromatic amino alkyne, named Sourin. Conclusion : Streptomyces-produced 08346 strain demonstrates good antimicrobial activities against bacteria and yeasts, suggesting its potential as an antimicrobial membrane-active agent. Keywords: Actinomycetes, Secondary metabolites, Streptomycetes, Membrane-active agent

Identification and Evaluation of Novel Drug Targets against the Human Fungal Pathogen Aspergillus fumigatus with Elaboration on the Possible Role of RNA-Binding Protein

Bakground: Aspergillus fumigatus is an airborne opportunistic fungal pathogen that can cause fatal infections in immunocompromised patients. Although the current anti-fungal therapies are relatively efficient, some issues such as drug toxicity, drug interactions, and the emergence of drug-resistant fungi have promoted the intense research toward finding the novel drug targets. Methods: In search of new antifungal drug targets, we have used a bioinformatics approach to identify novel drug targets. We compared the whole proteome of this organism with yeast Saccharomyces cerevisiae to come up with 153 specific proteins. Further screening of these proteins revealed 50 potential molecular targets in A. fumigatus. Amongst them, RNA-binding protein (RBP) was selected for further examination. The aspergillus fumigatus RBP (AfuRBP), as a peptidylprolyl isomerase, was evaluated by homology modeling and bioinformatics tools. RBP-deficient mutant strains of A. fumigatus were generated and characterized. Furthermore, the susceptibility of these strains to known peptidylprolyl isomerase inhibitors was assessed. Results: AfuRBP-deficient mutants demonstrated a normal growth phenotype. MIC assay results using inhibitors of peptidylprolyl isomerase confirmed a higher sensitivity of these mutants compared to the wild type. Conclusion: Our bioinformatics approach revealed a number of fungal-specific proteins that may be considered as new targets for drug discovery purposes. Peptidylprolyl isomerase, as a possible drug target, was evaluated against two potential inhibitors, and the promising results were investigated mechanistically. Future studies would confirm the impact of such target on the antifungal discovery investigations