The efficacy of successful cancer therapies is frequently hindered by the development of drug resistance in the tumor. The term 'drug resistance' is used to illustrate the decreased effectiveness of a drug in curing a disease or alleviating the symptoms of the patient. This phenomenon helps tumors to survive the damage caused by a specific drug or group of drugs. In this context, studying the mechanisms of drug resistance and applying this information to design customized treatment regimens can improve therapeutic efficacy as well as the curative outcome. Over the years, numerous multidrug resistance (MDR) mechanisms have been recognized and tremendous effort has been put into developing agents to address them. The integration of data emerging from the elucidation of molecular and biochemical pathways and specific tumor-associated factors has shown tremendous promise within the oncology community for improving patient outcomes. In this review, we provide an overview of the utility of these molecular and biochemical signaling processes as well as tumor-associated factors associated with MDR, for the rational selection of cancer treatment strategies.

In our continued efforts to find potential chemotherapeutics active against drug-resistant (DR) Mycobacterium tuberculosis (Mtb), causative agent of Tuberculosis (TB) and to curb the current burdensome treatment regimen, herein we describe the synthesis and biological evaluation of urea and thiourea variants of 5-phenyl-3-isoxazolecarboxylic acid methyl esters as promising anti-TB agent. Majority of the tested compounds displayed potent in vitro activity not only against drug-susceptible (DS) Mtb H37Rv but also against drug-resistant (DR) Mtb. Cell viability test against Vero cells deemed these compounds devoid of significant toxicity. 3,4-Dichlorophenyl derivative (MIC 0.25 µg/mL) and 4-chlorophenyl congener (MIC 1 µg/mL) among urea and thiourea libraries respectively exhibited optimum potency. Lead optimization resulted in the identification of 1,4-linked analogue of 3,4-dichlorophenyl urea derivative demonstrating improved selectivity. Further, in silico study complemented with previously proposed prodrug like attributes of isoxazole esters. Taken together, this molecular hybridization approach presents a new chemotype having potential to be translated into an alternate anti-Mtb agent. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10543-0.

The urgent development of newer alternatives has been deemed a panacea for tackling emerging antimicrobial resistance effectively. Herein, we report the design, synthesis, and biological evaluation of 1,3-diaryl substituted pyrazole-based...

In recent past, repurposing and subsequent medicinal chemistry efforts on anti‐obesity drug rimonabant has successfully delivered several pyrroles and pyrazole‐based hits active against Mycobacterium tuberculosis (Mtb). Herein, we report the synthesis and biological evaluation of a new series of 1,3‐substituted pyrazole containing carboxamide derivatives as potential antitubercular (anti‐TB) agents. Preliminary screening indicated substantial potency and selectivity towards Mtb H37Rv. Lead compounds when subjected to cell viability test demonstrated low cytotoxicity. Structural optimization of the most active compound (MIC 0.06 μg/mL) led to the identification of 3‐heteroaromatic substituted pyrazole derivatives amongst which the lead compound exhibited equipotent activity (MIC 0.03 μg/mL) against both drug‐susceptible (DS) and drug‐resistant (DR) Mtb besides high selectivity index (SI>333). Further, time‐kill assay found these optimum active compounds endowed with mycobactericidal efficacy. Potent in vitro activity, high selectivity along with mycobactericidal attributes establishes lead compounds of the series as promising antimycobacterial candidates for further development.