Design, Synthesis, and Antibacterial and Antifungal Activities of Novel Trifluoromethyl and Trifluoromethoxy Substituted Chalcone Derivatives.

Surendra Babu Lagu,Afzal B Shaik,Rajendra Prasad Yejella,Richie R Bhandare

doi:10.3390/ph13110375

Abstract

Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections.

Highlights

Infectious diseases in human beings are caused by microbes including bacteria, fungi, and viruses
The two series of chalcones were afforded by the Claisen–Schmidt condensation reaction of substituted aryl and unsubstituted heteroaryl aldehydes with two different types of ketones, i.e., 4 -trifluoromethyl acetophenone and 4 -trifluoromethoxy acetophenone
Against Escherichia coli and Proteus vulgaris, A3 was 7.64 times more active than benzyl penicillin whereas B3 was 7.95 and 3.97 times more active. These results show that the activity of A3 containing a trifluoromethyl group favored the Gram-negative bacteria and B3 with a trifluoromethoxy group favored Gram-positive bacteria

Summary

Introduction

Infectious diseases in human beings are caused by microbes including bacteria, fungi, and viruses. These diseases are treated by employing a range of antimicrobials available in the market. Resistance to antimicrobial agents is a major threat to public health and is responsible for significant rise in morbidity, mortality, and hospitalization. Keeping this in view, World Health Organization (WHO) introduced a preamble “no action today no cure tomorrow” to counteract the trouble of AMR [3,4,5]. Screening of small molecule libraries derived through laboratory synthesis is widely employed in the pharmaceutical industry to identify lead molecules with potential drug-like properties [9]

Methods

Results

Conclusion