Chinese Chemical Letters
Original article
Facile synthesis of benzimidazole bearing 2-pyridone derivatives as
potential antimicrobial agents
*
N.C. Desai , N.R. Shihory, G.M. Kotadiya
Division of Medicinal Chemistry, Department of Chemistry (UGC NON-SAP & DST-FIST Sponsored), M.K. Bhavnagar University, Bhavnagar 364 002, India
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of benzimidazole bearing 2-pyridones 5a–k were synthesized and assessed in vitro for their
activity as antimicrobial agents using the conventional broth dilution method. The results of the
antimicrobial study revealed that compounds 5b, 5c, 5j and 5k exhibited substantial antibacterial
activity while compound 5d emerged as amore potent antifungal agent compared to the standard drugs
chloramphenicol and ketoconazole, respectively. It was observed that the presence of inductively
electron withdrawing groups remarkably enhance the antibacterial activity of the newly synthesized
compounds. Cytotoxicity studies suggested that none of the tested compounds exhibited any significant
cytotoxic effects.
Received 29 July 2013
Received in revised form 24 October 2013
Accepted 4 November 2013
Available online 19 November 2013
Keywords:
Benzimidazole
2-Pyridone
ß 2013 N.C. Desai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Antimicrobial activity
Cytotoxicity
1. Introduction
possessed favorable pharmacokinetic properties and lipophilicity
that influence the ability of drug to reach the target by
The alarming rate of emerging and reemerging microbial threat
of bacterial resistance has heightened the urgency to discover and
develop effective agents with novel mechanisms of action and
enhanced activity. Despite the development of several new
antibacterial agents, their clinical value is limited in treating an
increasing array of life threatening systemic infections. Thus, the
development of potent and effective antimicrobial agents is most
important to overcome the emerging multi-drug resistance strains
of bacteria and fungi.
2-Pyridones represent a unique class of pharmacophores, which
are observed in various antibiotics and therapeutic agents [1]. In
recent years, 2-pyridones have been found to exhibit several
biological activities, such as analgesic [2], anti-HIV [3] and
antitumoral [4] properties. Moreover, 2-pyridones are a class of
recently discovered potent antibacterial agents that are of
particular interest due to their in vitro and in vivo antibacterial
potency against the bacterial type II DNA topoisomerases, which
include two highly homologous enzymes-DNA gyrase and
topoisomerase IV [5]. In addition, benzimidazoles are considered
transmembrane diffusion and showed promising activity against
resistant TB by inhibiting the biosynthesis of lipids [10].
Molecular hybridization is an important tool for discovery of
new chemical entities. In the past several decades much attention
has been given to the design and synthesis of new types of
pharmacologically diverse structural hybrid molecules [11]. One
shining example is vilazodone, which combined serotonin reup-
take inhibitor (SSRI) and 5-HT1A receptor partial agonist and was
marketed under the tread name Viibryd [12]. Motivated by the
above findings and our previous work [13,14], it was thought
worthwhile to synthesize new benzimidazole bearing 2-pyridone
derivatives 5a–k that contain the aforementioned moieties in a
single molecular framework in order to investigate their in vitro
antibacterial and antifungal activity.
2. Experimental
Elemental analysis (% C, H, N) was carried out by a Perkin-Elmer
2400 CHN analyzer. IR spectra of all compounds were recorded on
a Perkin-Elmer FT-IR spectrophotometer in KBr. 1H NMR spectra
were recorded on a Varian Gemini 300 MHz and 13C NMR spectra
on a Varian Mercury-400, 100 MHz in DMSO-d6 as a solvent and
tetramethylsilane (TMS) as an internal standard. Mass spectra
were scanned on a Shimadzu LC–MS 2010 spectrometer.
as
a promising class of bioactive heterocyclic compounds
surrounding a diverse range of biological activities such as
antihypertensive [6], anticoagulant [7], anti-inflammatory [8]
and antimicrobial [9]. The azole group of heterocyclic compounds
General procedure for the synthesis of title compounds 5a–k:
Compound 4 (0.01 mol), different substituted aromatic aldehydes
(0.01 mol) and ethanol (50 mL) were taken in a round bottom flask
and refluxed for 5 h. After 5 h, the reaction mass was poured onto
*
Corresponding author.
(N.C. Desai).
1001-8417/$ – see front matter ß 2013 N.C. Desai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Desai
