Vol.:(0123456789) 1 3 Journal of the Iranian Chemical Society (2018) 15:621–628 https://doi.org/10.1007/s13738-017-1262-2 ORIGINAL PAPER Virtual screening of some heterocyclic structures toward novel antibacterial agents Zahra S. Hosseini 1  · Mohammad Reza Housaindokht 1  · Nima Razzaghi‑Asl 2  · Ramin Miri 3 Received: 30 April 2017 / Accepted: 30 November 2017 / Published online: 4 December 2017 © Iranian Chemical Society 2017 Abstract Infectious diseases and their treatment are among the most important issues in global health and economy. Moreover, increas- ing prevalence of antibiotic-resistant pathogenic bacteria necessitates the considerable need for discovering new drugs. Some heterocyclic structures with dihydropyridine (DHP) scafold have been reported as antimicrobial agents. Herein, we report a structure-based virtual screening of a pool of 3,5-disubstituted DHPs and a post-analysis of virtual hits through in vitro antibacterial assessment. Four top-ranked DHP structures (6a–d) were found to interact with the relevant target active sites and exhibited superior stereoelectronic features within their enzyme inhibition. Selected compounds were synthesized and assessed for their antibacterial activity via microdilution method. Results of this study represented a signifcant application of multi-step virtual screening strategy in identifying privileged DHP structures as good starting points for further develop- ments toward more potent antibacterial agents. Keywords Antibiotic resistance · Dihydropyridine · Docking · Virtual screening · In vitro Introduction The remarkable role of bacterial infections in mortality has become a big concern and human life has been always asso- ciated with risks related to such infectious diseases. During the past century, many prosperous eforts have been per- formed to control infectious diseases, but the prevention and treatment of infectious diseases still remained a serious problem in public health, leading to over 13 million deaths each year [1]. Within antimicrobial therapy, antibiotic resist- ance is one of the major challenges and is usually considered to be a consequence of antibiotic misuse. Nowadays, many of bacteria are resistant to at least one of the most commonly used drugs. Therefore, existing drugs can’t properly respond to the control and treatment of many infectious diseases, and hence, design and development of new and more efective antibacterial agents are an urgent requirement in human life [2]. Considerable advances in the field of computational chemistry and protein crystallography facilitated most of the traditional eforts toward discovery of novel chemo- therapeutic agents [3]. In silico or computer-aided drug design is a rational drug discovery technique that serves as a fundamental part of modern drug discovery projects. In this regard, one of the most efcient strategies is virtual screening (VS) of chemical databases with the aim of fnd- ing novel bioactive compounds [4]. Virtual screening tries to efciently reduce the defned chemical space to a much smaller subset that can be synthesized and assessed through biological targets with the aim of achieving potential lead/ drug candidates. It has been postulated that VS can reduce costs and increase hit rates in a typical lead discovery path [5] and therefore may be an alternative approach to high- throughput screening (HTS) [6]. Structure-based virtual screening (SBVS) utilizes dock- ing algorithms to explore the conformational space of ligand–receptor complex [7]. The outputs are top-ranked Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13738-017-1262-2) contains supplementary material, which is available to authorized users. * Mohammad Reza Housaindokht housain@um.ac.ir 1 Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran 2 Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran 3 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran