Current Topics in Medicinal Chemistry          Michelyne Haroun a,* , Christophe Tratrat a , Katerina Kositzi b , Evangelia Tsolaki b , Anthi Petrou b , Bandar Aldhubiab a , Mahesh Attimarad a , Sree Harsha a , Athina Geronikaki b,* , Katharigatta N. Venugopala a,c , Heba S. Elsewedy a , Marina Sokovic d , Jasna Glamoclija d and Ana Ciric d a Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia; b Aristotle University, School of Pharmacy, Thessaloniki, 54124, Greece; c Department of Biotechnology and Food Technology, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa; d My- cological Laboratory, Department of Plant Physiology, Institute for Biological Research, Siniša Stanković, University of Belgrade, Bulevar DespotaStefana 142, 11000, Belgrade, Serbia A R T I C L E H I S T O R Y Received: November 13, 2017 Revised: November 17, 2017 Accepted: November 22, 2017 DOI: 10.2174/1568026618666180206101814 Abstract: Background: Thiazole and benzothiazole derivatives, as well as thiazolidinones are very im- portant scaffolds in medicinal chemistry. Literature has revealed that they possess a wide spectrum of biological activities including antimicrobial activity. Objective: The goal of this paper is the designing of new benzothiazole based thiazolidinones and the evaluation of their biological activities. Methods: The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was evaluated using the method of microdilution. Results: The twelve newly synthesized compounds showed antimicrobial properties. All compounds appeared to be more active than ampicillin in most studied strains and in some cases, more active than streptomycin. Antifungal activity, in most cases was also better than the reference drugs ketoconazole and bifonazole. The prediction of cytotoxicity revealed that the synthesized compounds were not toxic (LD50 350-1000 mg/kg of body weight). Docking studies on the antibacterial activity confirmed the biological results. Conclusion: The twelve new compounds were synthesized and studied for their antimicrobial activity. The compounds appeared to be promising antimicrobial agents and could be the lead compounds for new, more potent drugs. According to the docking prediction, the compounds could be MurB inhibitors. Keywords: Benzothiazole, Thiazolidinone, Antibacterial, Antifungal, Microdilution, Drugs. 1. INTRODUCTION The term infection describes the entry of microbes in the body, their installation in places where they are endemic and the consequent cause of inflammatory reaction through their toxicity. Despite that, the discovery of antimicrobial agents during the 20th centuryhas substantially reduced the threats posed by infectious diseases. Due to the large number of antibiotics and chemotherapeutics available, the appearance of resistant strains led to the urgent need for the development of new antimicrobials with different modes of action. Taking into account the growing problem of resistance to antimicrobials, the World Health Organization in newsletter *Address correspondence to these authors at the Department of Pharmaceu- tical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Tel.: +966550909890, E-mail: michelineharoun@gmail.com; mharoun@kfu.edu.sa and Aristotle University of Thessaloniki, School of Pharmacy, Thessaloniki, 54124, Greece; Tel.: 30 2310997616; E-mail: geronik@pharm.auth.gr No194 (2015) reported that resistance to antibiotics is no longer a forecast for the future and that without concerted action, the world is heading towards a “post-antibiotic era” in which common infections and minor injuries which have been treatable for decades, could still be a mortal danger. Thiazolyl and benzothiazolyl derivatives have been found to possess analgesic, [1, 2] anti-inflammatory, [3-5] antioxidant, [5,6], cycloxygenase and lipoxygenase inhibi- tory [7-9] as well as antimicrobial activities [10-16]. Thiazolidinone is an interesting core responsible for nu- merous types of biological activities and pharmacological properties such as antimicrobial, [17-25] anti-inflammatory and analgesic [26, 27], anti-viral [28-30], antioxidant, [31, 32] anticancer [32-34], antidiabetic [35] and anticonvulsant [36]. Taking all of these into account and as a continuation of our attempts in developing new antimicrobial agents [12-16, 20, 21, 24], we hereby, reported the synthesis of 6- methoxybenzothiazol- 2-thiazolylimino-5-arylidene-4-thiaz- 1873-4294/18 $58.00+.00 © 2018 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.ae Current Topics in Medicinal Chemistry, 2018, 18, 75-87 75 RESEARCH ARTICLE New Benzothiazole-based Thiazolidinones as Potent Antimicrobial Agents. Design, Synthesis and Biological Evaluation