Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities.

Afzal B Shaik,Zehra Edis,M Mukhlesur Rahman,Richie R Bhandare,Srinath Nissankararao,Shaik Shahanaaz,N Ravikiran Tangirala

doi:10.3390/molecules25143188

Abstract

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC50 value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities.

Highlights

Chalcones are a class of natural products characterized by the presence of two aromatic rings connected through α,β-unsaturated ketone moiety
As a research part of our well as information published in the literature and our previously reported work, here we report the design based on the information published in the literature and our previously reported work, here we report anddesign facile and synthesis dichloro‐substituted chalcones chalcones and dihydropyrazoles (Figure 3) (Figure for their3) for the facile of synthesis of dichloro-substituted and dihydropyrazoles antifungal, anti‐tubercular and antiproliferative activities
We reported the antifungal, antitubercular, and antiproliferative activity and structure–activity relationship of 30 dichlorophenyl ring-containing compounds including

Summary

Introduction

Chalcones are a class of natural products characterized by the presence of two aromatic rings connected through α,β-unsaturated ketone moiety. These are a type of 1,3-diphenyl-2-propene1-ones which serve as precursors for the synthesis of different classes of flavonoids and isoflavonoids—a. Chalcones are a class of natural products characterized by the presence of two aromatic rings α,β‐unsaturated ketone moiety. Propene‐1‐ones which serve as precursors for the synthesis of different classes of flavonoids and isoflavonoids—a class of biologically important of natural products. The α,β‐unsaturated ketone class of biologically important of natural products.

Methods

Results

Conclusion