ANTIMICROBIAL INVESTIGATION AND BINDING MODE ANALYSIS OF SOME NEWLY SYNTHESIZED 4-AMINO-5-((ARYL SUBSTITUTED)-4H-1, 2, 4-TRIAZOLE-3-YL)-THIO LINKED HYDROXAMIC ACID DERIVATIVES

SUBHASIS BANERJEE,ARNAB DE,AMALESH SAMANTA,BHASKAR DAS,MOUSUMI DAS

doi:10.22159/ajpcr.2019.v12i3.30882

SUBHASIS BANERJEE, ARNAB DE + Show 3 more

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https://doi.org/10.22159/ajpcr.2019.v12i3.30882

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Abstract

Objective: A series of 5-substituted-4-amino-1, 2, 4-triazole-linked hydroxamic acid derivatives have been synthesized and explored in vitro to evaluate antibacterial and antifungal activities. Methods: Different 5-phenyl group substituted-4-amino-1,2,4-triazole-3-thiol reacted with chlorine substituted hydroxamic acid to produce the desired compounds and characterized spectroscopically. Minimum inhibitory concentration (MIC), zone of inhibition (ZOI), growth kinetic studies, and scanning electron microscopy (SEM) were employed to elicit the antimicrobial efficacy of synthesized compounds against a wide range of bacterial and fungal strains. Results: Compounds 6a, 6b, 6d, and 6k (MIC of 25 μg/ml) have been found to be more potent against Klebsiella pneumoniae, Bacillus cereus, Bacillus pumilus, Micrococcus luteus, and Pseudomonas aeruginosa, compounds 6a-6d, 6k, and 6l (MIC of 25–50 μg/ml) have shown potent antibacterial efficacy against Klebsiella pneumonia, P. aeruginosa, and Vibrio cholera compare to the standard drug amoxicillin (MIC of 60 μg/ml, 65 μg/ml, and 25 μg/ml, respectively). Screening for the antifungal activity revealed that the compounds were found to be most active against Candida albicans (6a, 6b, and 6l), Candida tropicalis (6b and 6d), and Aspergillus niger (6a, 6b, 6d, and 6j) with MIC of 15–25 μg/ml. Bacteriostatic and fungistatic effect of titled compounds was revealed from growth kinetics study. Conclusion: Electron donating group at the 5-position of the 5-substituted-1,2,4-triazole-linked hydroxamic acid derivatives conferred the biological effectiveness of the synthesized compounds and also offer a therapeutically effective prototypical structure for further development of new chemical entities with superior antimicrobial activity.

Highlights

The microbes are getting resistant toward the existing chemotherapeutics in alarming rate which is a major concern for public health and a challenge for the scientific community globally, and the number of cases of multidrug-resistant bacterial infections is increasing nowadays [1]
Azole compounds showed the effect by inhibiting lanosterol 14α-demethylase (CYP51) which catalyzes the oxidative removal of the 14α-methyl group of lanosterol to give Δ14,15desaturated intermediates in ergosterol biosynthesis [3] resulting in accumulation of toxic methyl-sterols in membranes leading to fungistatic or fungicidal effect [4]
The Fourier-transform infrared (FT-IR) spectra were measured in Nicolet iS10 FT-IR Spectrometer (Thermo Fisher Scientific, USA), 1H nuclear magnetic resonance (NMR) spectra were recorded on AV300 Digital FT NMR Spectrometer, Bruker at 300 MHz using dimethyl sulfoxide (DMSO)-d6 as the solvent and tetramethylsilane as an internal standard, 13C NMR spectra were obtained at 500 MHz (Bruker, Germany), DMSO-d6 as the solvent

Summary

Introduction

The microbes are getting resistant toward the existing chemotherapeutics in alarming rate which is a major concern for public health and a challenge for the scientific community globally, and the number of cases of multidrug-resistant bacterial infections is increasing nowadays [1]. The infections caused by the Grampositive bacteria are very common. The infection caused by them is sometime severe. Staphylococcus aureus, Bordetella bronchiseptica, Micrococcus luteus, Bacillus pumilus, Bacillus subtilis, and Enterococcus faecalis are some important Gram-positive bacteria causing serious infection in the community, whereas Salmonella typhi, Klebsiella pneumoniae, Vibrio cholerae, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium are very common Gramnegative bacteria. The mortality is higher for infections caused by Gram-negative bacteria than the Gram-positive one. Some important azoles derivatives such as voriconazole, itraconazole, posaconazole, and fluconazole (Fluc) are used for the treatment of fast-growing fungal infections, which are the leading cause of mortality and morbidity in immunocompromised patients [5]. Fluc is not effective against aspergillosis due to its severe drug resistance [6,7]

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