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Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives.

ABSTRACT: Azole-based antifungal agents constitute one of the important classes of antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole derivatives 3a-3l were synthesized to evaluate their anticandidal activity against C.albicans, C.glabrata, C.krusei, and C.parapsilopsis. The structures of the newly synthesized compounds 3a-3l were confirmed by IR, ¹H-NMR, 13C-NMR, and ESI-MS spectroscopic methods. ADME parameters of synthesized compounds 3a-3l were predicted by an in-slico study and it was determined that all synthesized compounds may have a good pharmacokinetic profile. In the anticandidal activity studies, compounds 3c and 3d were found to be the most active compounds against all Candida species. In addition, cytoxicity studies showed that these compounds are nontoxic with a IC50 value higher than 500 µg/mL. The effect of compounds 3c and 3d on the ergosterol level of C.albicans was determined by an LC-MS-MS method. It was observed that both compounds cause a decrease in the ergosterol level. A molecular docking study including binding modes of 3c to lanosterol 14?-demethylase (CYP51), a key enzyme in ergosterol biosynthesis, was performed to elucidate the mechanism of the antifungal action. The docking studies revealed that there is a strong interaction between CYP51 and the most active compound 3c.

SUBMITTER: Kaplanc?kl? ZA

PROVIDER: S-EPMC6149685 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives.

Kaplancıklı Zafer Asım ZA Levent Serkan S Osmaniye Derya D Sağlık Begüm Nurpelin BN Çevik Ulviye Acar UA Çavuşoğlu Betül Kaya BK Özkay Yusuf Y Ilgın Sinem S

Molecules (Basel, Switzerland) 20171123 12

Azole-based antifungal agents constitute one of the important classes of antifungal drugs. Hence, in the present work, 12 new benzimidazole-thiazole derivatives 3a-3l were synthesized to evaluate their anticandidal activity against C.albicans, C.glabrata, C.krusei, and C.parapsilopsis. The structures of the newly synthesized compounds 3a-3l were confirmed by IR, ¹H-NMR, 13C-NMR, and ESI-MS spect ...[more]

PMID: 29168743

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Project description:A series of Schiff bases (3.a-f) bearing benzimidazole moiety was successfully synthesized in ethanol by refluxing Oct-2-ynoic acid (1,3-dihydrobenzimidazole-2-ylidene)amide with substituted amines. Fourier transform infrared (FTIR), ultra violet light (UV-VIS), elemental analysis, proton (1H) and carbon (13C) nuclear magnetic resonance spectroscopy were used to characterize the newly synthesized Schiff bases. Micro dilution method was used to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of the Schiff bases, against 14 human pathogenic bacteria (8 Gram negative and 6 Gram positive) and against 7 fungal strains (5 Aspergillus and 2 Fusarium) representatives. Antimalarial activity against Plasmodium falciparum and antitrypanosomal property against Trypanosoma brucei was studied in vitro at a single dose concentration of the Schiff bases. Cytotoxicity of the Schiff bases was assessed against human cervix adenocarcinoma (HeLa) cells. Results obtained show that the newly synthesized Schiff bases are very potent antimicrobial agents. Gram negative bacteria Klebsiella pneumonia and Escherichia coli were more affected on exposure to Compounds 3.c-f (MIC 7.8 µg/mL) which in turn exhibited more antibacterial potency than nalidixic acid reference drug that displayed MICs between 64 and 512 µg/mL against K. pneumonia and E. coli respectively. The test compounds also demonstrated high cytotoxic effect against Aspergillus flavus and Aspergillus carbonarius as they displayed MFC 7.8 and 15.6 µg/mL. Compound 3.c exhibited the highest fungicidal property from this series with MFC alternating between 7.8 and 15.6 µg/mL against the investigated strains. The malarial activity revealed Compounds 3.c and 3.d as the more potent antiplasmodial compounds in this group exhibiting 95% and 85% growth inhibition respectively. The IC50 of Compounds 3.c and 3.d were determined and found to be IC50 26.96 and 28.31 µg/mL respectively. Compound 3.a was the most cytotoxic agent against HeLa cells in this group with 48% cell growth inhibition. Compounds 3.c, 3.d and 3.f were biocompatible with HeLa cells and displayed low toxicity. With a very low cytotoxic effect against HeLa, compound 3.c stands out to be a very good antiparasitic agent and consideration to further evaluate the candidate drug against others cell lines is necessary.

Dataset Information

Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives.

Publications

Synthesis and Anticandidal Activity Evaluation of New Benzimidazole-Thiazole Derivatives.

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