Phenylsulfonyl piperazine bridged [1,3]dioxolo[4,5-g]chromenones as promising antiproliferative and antioxidant agents

• Published in: Bioorganic chemistry Vol. 87; pp. 23 - 30
• Main Authors: Patel, Rahul V., Mistry, Bhupendra M., Syed, Riyaz, Parekh, Nikhil M., Shin, Han-Seung
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.06.2019; Elsevier
• Subjects: Antioxidant; Antiproliferative; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Chromenones; Free radicals; Homoisoflavonoids; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; Sulfonylpiperazines; Antiproliferative; Sulfonylpiperazines; Free radicals; Antioxidant; Chromenones; Homoisoflavonoids; MECHANISM; CHROMAN-4-ONE; FLUORINE; EXTRACTS; DERIVATIVES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.03.002

Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl and chalcone bridge representing flavones or homoisoflavonoids and in vitro antioxidant and anticancer properties were investigated. [Display omitted] •[1,3]dioxolo[4,5-g]chromenones were inspected for pharmacological properties.•Presence of EWD and ED substituents displayed varied and promising IC50 data.•OCF3 and OCH3 played a crucial role against DPPH, ABTS+, SK-OV-3 and HT-29.•Halogen atom(s) attributed excellent inhibitory potential against HeLa and A-549.•Promising activities warrant further studies for the structural optimization. Two series of sulfonylpiperazines linked [1,3]dioxolo[4,5-g]chromenones were synthesized featuring phenyl (7a-k) and chalcone (12a-k) bridge representing flavones or homoisoflavonoids core. New molecules are synthesized utilizing aldol condensation to inspect as antioxidants against DPPH and ABTS+ and antiproliferative agents toward selected human cancer cell lines. Cytotoxicity of new compounds was confirmed using SRB assay against non-cancer MDCK cell line. The results concluded that both individual structures of 7 and 12 were vital for modulating pharmacological potencies and presence of different electron withdrawing and electron donating functional group(s) on the phenylsulfonyl entity yielded varied biological effects. Substituent h (OCF3) and j, k (OCH3) were found to play a crucial role scavenging DPPH and ABTS+ as well as inhibiting cancer cell lines SK-OV-3 and HT-29. Moreover, molecules bearing halogen atom(s) such as substituent b-g expressed excellent inhibitory potential against HeLa and A-549 cancerous cell lines. Bioassay data displayed some interesting structure-activity relationships which are discussed in this paper. The results justified that tested derivatives are promising antioxidants and cytotoxic agents and warrant further structural optimization and bioassay studies. Spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and elemental analysis (CHN) were carried out to confirm the final structures.