Original Article DESIGN, SYNTHESIS, DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 2-PHENYL-3- (SUBSTITUTED BENZO[d] THIAZOL-2-YLAMINO)-QUINAZOLINE-4(3H)-ONE DERIVATIVES AS ANTIMICROBIAL AGENTS POOJA PISAL, MEENAKSHI DEODHAR, AMOL KALE, GANESH NIGADE, SMITA PAWAR * Department of Pharmaceutical Chemistry, PDEA’s Seth Govind Raghunath Sable College of Pharmacy, Saswad, Pune 412301, India Email: sjpawar4477@gmail.com Received: 13 Jul 2018 Revised and Accepted: 01 Sep 2018 ABSTRACT Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi. Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable. Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 µg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 µg/ml MIC. Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent. Keywords: Benzothiazole, Benzoxazine, Quinazoline, Antimicrobials © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijpps.2018v10i10.28480 INTRODUCTION There has been a continual encounter between human and the multitude of microorganism that cause infection and disease. Recently it has been evidenced that there is an insistent increase in antibiotic resistance to many common bacterial pathogens such as Staphylococcus aureus. The number of cases of multidrug-resistant bacterial infections is increasing day by day. This situation requires the design of novel antimicrobial agents acting on novel targets. Benzothiazole derivatives show numerous biological activities such as antimicrobial [1], anticancer [2], antileishmanial [3], anti-diabetic and antifungal [4] activities. In recent years’ heterocyclic compounds and derivatives have attracted strong interest due to their biological and pharmacological properties. Substituted quinazoline-4-one have been shown to possess antibacterial, antifungal and antimicrobial activity [5-7]. Thus, it is revealed from the literature that benzothiazole, as well as quinazolin-4-one derivatives, hold diverse pharmacological activity. DNA gyrase is a bacterial enzyme that catalyzes the introduction of negative supercoils in a closed-circular DNA using the energy of the ATP hydrolysis. Since it was found only in prokaryotes and is vital for their survival; it has become an attractive target for antibacterial agents [8]. Benzothiazole and quinazoline derivatives were known to possess DNA gyrase inhibitory activity [9]. Thus, we thought to incorporate both leads together with the hope to have better antimicrobial potential. Thus, this paper reports the synthesis and antimicrobial activity of 2-phenyl-3-(substituted benzo [d] thiazol-2-ylamino)-2-phenyl- quinazolin-4(3H)-one. The molecular docking studies were also carried out to check the possible interactions of compounds with DNA gyrase active pocket. MATERIALS AND METHODS All the reagents and chemicals used were of analytical grade. The progress of the reaction and purity of all the synthesized compounds was monitored by TLC. IR spectra were recorded on Shimadzu FTIR 8400S by using KBr, and the NMR spectra were recorded in NMR Varian-Mercury 300 MHz spectrometer in CDCl3 and values are expressed in ppm. Antimicrobial activity Zone of inhibition The compounds were evaluated for the antibacterial activity by the cup, plate method against gram-positive bacteria S. aureus (ATCC 9144) B. subtilis (ATCC 6633) and gram-negative bacteria E. coli (ATCC 25922), P. aeruginosa (ATCC 9027) and A. Niger (ATCC 16404) and C. albicans (ATCC 10231), at the concentration: 50 μg/ml, 100 μg/ml, 150 μg/ml. The bacterial strains were obtained from NCL, and fungal strains were obtained from the microbiology department of Waghire College, Saswad. The ciprofloxacin 150 μg/ml and 150 μg/ml of fluconazole were used as reference drugs for antibacterial and antifungal study respectively. The bacteria were sub-cultured in the nutrient agar medium containing peptone (1%), beef extract (0.5%), sodium chloride (0.8%) and agar (2.5%), in distilled water. The solution was sterilized for 20 min at 15 psi pressure in an autoclave at 120 °C. The basal medium 15-20 ml was poured into the sterile Petri dishes. After the solidification of the medium, the suspension of the organism was spread by the spreader and holes of 6 mm diameter were bored to form cups with the help of a sterile cork borer. In this cup 20 μl of 50 μg/ml, 100 μg/ml, 150 μg/ml (solvent DMSO) of the test compounds were added by the micropipette. The zone of inhibition was measured in mm after incubation at 37 °C for 48 h. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 10, Issue 10, 2018