Send Orders for Reprints to reprints@benthamscience.ae Letters in Drug Design & Discovery, 2021, 18, 1-9 1 RESEARCH ARTICLE 1570-1808/21 $65.00+.00 ©2021 Bentham Science Publishers Chalcones and Bis-Chalcones Analogs as DPPH and ABTS Radical Scavengers Adebayo Tajudeen Bale 1,2 , Uzma Salar 3 , Khalid Mohammed Khan 1,4,* , Sridevi Chigurupati 5 , Tolulope Fasina 2 , Farman Ali 1 , Muhammad Ali 1 , Sitanshu Sekhar Nanda 6 , Muhammad Taha 4 and Shahnaz Perveen 7 1 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; 2 Department of Chemistry, University of Lagos. Nigeria; 3 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; 4 Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia; 5 Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia; 6 Department of Chemistry, Myongji University, Yongin, South Korea; 7 PCSIR, Laboratories complex, Shahrah-e- Dr. Salimuzzaman, Karachi- 75280, Pakistan Abstract: Background: A number of synthetic scaffolds, along with natural products, have been identified as potent antioxidants. The present study deals with the evaluation of varyingly substituted, medicinally distinct class of compounds “chalcones and bis-chalcones” for their antioxidant potential. Methods: In vitro radical scavenging activities were performed on a series of synthetic chalcones 1- 13 and bis-chalcones 14-18. Results: All molecules 1-18 revealed a pronounced 2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ- azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals scavenging potential in the ranges of IC 50s = 0.58 ± 0.14 - 1.72 ± 0.03 and 0.49 ± 0.3 - 1.48 ± 0.06 µM, respectively. Ascorbic acid (IC 50s = 0.5 ± 0.1 and 0.46 ± 0.17 µM for DPPH and ABTS, respectively) was used as a stan- dard radical scavenger. Conclusion: Structure-activity relationship (SAR) revealed an active participation of various groups, including -SMe and -OMe in scavenging activity. Keywords: Chalcones, bis-chalcones, reactive oxygen species (ROS), DPPH, ABTS, in vitro. 1. INTRODUCTION Free radicals (FRs) are known to be highly reactive spe- cies, possessing one or more ‘unpaired’ electron in their last atomic or molecular orbital. Oxygen-based FRs are highly important in biochemical processes. These oxygen FRs in- clude superoxide (O 2 - ), alkoxyl (RO • ), peroxyl (ROO • ), hy- droxyl ( • OH), and hydroperoxyl (HOO • ) radicals. • OH and HOO • radicals normally result from the homolytic fission of hydrogen peroxide (H 2 O 2 ). There are several non-radical reactive oxygen-based species of biological interest such as singlet oxygen ( 1 O 2 ), hypochlorous acid (HOCl), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), and peroxynitrite *Address correspondence to this author at the H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; Tel: 00922134824910; Fax: 00922134819018; E-mails: khalid.khan@iccs.edu; drkhalidhej@gmail.com (ONOO) [1, 2]. In the human body, several continuing bio- chemical reactions encompass through free-radical mecha- nisms. Oxidation, hydroxylation, and carboxylation are the biochemical processes that engage single-electron transfers from a cofactor or an FR intermediate. These FR intermedi- ates are associated with cytokine, ion transport, metabolic energy formation, neuro-modulation, growth factor, hormone action, RNA transcription, and programmed cell death [3]. Reactive oxygen species (ROS) are produced in the hu- man body from either exogenous or endogenous sources. Endogenously, ROS can be formed in soluble oxidase en- zyme systems, microsomal and mitochondrial electron trans- port systems, and during phagocyte activation [4]. However, exogenously, ROS can be generated from cigarette smoke, air pollutants, water pollutants, heavy metals, radiation, or- ganic solvents, and certain drugs, etc. [5]. Radical and non- radical based ROS, depending upon the concentration within the biological system, can either be toxic or advantageous. A R T I C L E H I S T O R Y Received: April 05, 2020 Revised: August 07, 2020 Accepted: August 24, 2020 DOI: 10.2174/1570180817999201001155032