Sulfonamide chalcones: Synthesis and in vitro exploration for therapeutic potential against Brugia malayi

• Published in: European journal of medicinal chemistry 2016-11, Vol.124, p.262-269
• Main Authors: Bahekar, Sandeep P., Hande, Sneha V., Agrawal, Nikita R., Chandak, Hemant S., Bhoj, Priyanka S., Goswami, Kalyan, Reddy, M.V.R.
• Format: Article
• Language: English
• Subjects: Animals; Antifilarial; Brugia malayi; Brugia malayi - drug effects; Brugia malayi - growth & development; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Chalcones - toxicity; Chemistry Techniques, Synthetic; Claisen-Schimdt condensation; Drug Design; Filaricides - chemical synthesis; Filaricides - chemistry; Filaricides - pharmacology; Filaricides - toxicity; Humans; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Life Cycle Stages; Models, Molecular; Molecular Conformation; Sulfonamide chalcone
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.08.042

Keeping in mind the immense biological potential of chalcones and sulfonamide scaffolds, a library of sulfonamide chalcones has been synthesized and evaluated for in vitro antifilarial assay against human lymphatic filarial parasite Brugia malayi. Experimental evidence showcased for the first time the potential of some sulfonamide chalcones as effective and safe antifilarial lead molecules against human lymphatic filarial parasite B. malayi. Sulfonamide chalcones 4d, 4p, 4q, 4t and 4aa displayed the significantly wide therapeutic window. Particularly chalcones with halogen substitution in aromatic ring proved to be potent antifilarial agents against Brugia malayi. Sulphonamide chalcones with lipophilic methyl moiety (4q and 4aa) at para position of terminal phenyl rings of compounds were found to have remarkable antifilarial activities with therapeutic efficacy. Observed preliminary evidence of apoptosis by effective chalcone derivatives envisaged its fair possibility to inhibit folate pathway with consequent defect in DNA synthesis. [Display omitted] •Synthesis and antifilarial assay of sulfonamide chalcones is reported.•In vitro cytotoxicity assay of effective compounds carried out on PBMCs.•Four of the thirteen effective compounds showed significant therapeutic window.•Chalcones possibly inhibit folate pathway with consequent defect in DNA synthesis.•Substitution with halogen and lipophilic methyl group proved to be effective.