Synthesis of 3-(1,3,4-Thiadiazole-2-yl)quinoline derivatives As Potential Antimicrobial Agents

Tazeem¹, Mohammad Arshad¹, Tuhfa, A.R. Bhat^2,3, Fareeda Athar^1,*

¹Centre for interdisciplinary research in basic sciences, Jamia Millia Islamia, New Delhi-110025

²School of Biotechnology, Yeungnum University, Gyeongsan 712-749, South Korea

³Department of Chemistry, Govt. Degree Collage Dooru, JKHED, Jammu and Kashmir-192211

Email: tazeemchem09@gmail.com

Abstract:

Problems of multidrug resistant microorganisms have reached up to an alarming level in the last few decades and globalization enhances the problem with the quick spread of such resistant microorganisms. Resistance to a number of antimicrobial agents, such as β-Lactam, Macrolides, Quinolones, Vancomycin etc., by the few clinically significant bacterial species, compounded the global problem. Heterocycles; especially azoles are widely exposed to the therapeutic world owing to their use in the treatment of many diseases such as malaria. Keeping an eye on the therapeutic effect of heterocyclic compounds, a series of 3-(1,3,4-Thiadiazole-2-yl)quinoline derivatives  and  their effect on  the  growth  of  microorganisms,  which  cause   microbial  infection  was  explored.  The  chemical structures of the compound were elucidated by elemental analysis, FTIR, ¹H and ¹³C NMR and ESI-MS spectral data. In vitro anti-microbial activity was performed against gram positive (Staphylococcus aureus and Streptococcus pyogenes) and gram negative (Salmonella typhimurium and Escherichia coli) bacteria. The MIC was detected using the serial dilution method. Equating the results with percent inhibited area/mg of the compounds and the standard “amoxicillin”, the compounds, N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-thiadiazole-2-yl)-N-cyclopentylacetamide and N-4-acetyl-5-(2-chloro-8-methyl quinolin-3-yl)-4,5-dihydro-1,3,4-thiadiazole-2-yl)-N-o-tolylacetamide showed better inhibition of S. pyogens whereas N-4-acetyl-5-(2,8-dichloroquinolin-3-yl)-4,5-dihydro-1,3,4-thiadiazole-2-yl)-N-o-tolyl acetamide and N-4-acetyl-5-(2-chloroquinolin-3-yl)-4,5-dihydro-1,3,4-thiadiazole-2-yl)-N-(2,5-difluoro phenyl)acetamide were better inhibitors  of  S. aureus than control (amoxicillin). To assess the toxic nature of the selected compounds, cell proliferation test was performed using MTT assay and H9c2 cardiac myoblasts cell line. The results showed that all the compounds offered remarkable >80% viability unto a concentration of 200 mg/ml.

Keywords: Chloroquinoline-3-carboxaldehyde, Thiosemicarbazone, Thiadiazole, Anti-microbial activity