Novel diastereoselective trans 2, 3-dihydrobenzofuran derivatives: Tandem synthesis, crystal structure, antioxidant and anticancer activity

Abstract

Tandem synthesis of three component aqueous mediated mild reaction protocol has been developed for the preparation of fused diastereoselective trans 2,3-dihydrobenzofuran derivatives (4a-k), (5a-h) & (6a-k). These compounds were characterized by 1H/13C NMR spectroscopy, mass spectrometry, and by single-crystal X-ray crystallography (6k). X-ray diffraction analysis shows that this material crystallizes in orthorhombic, space group P212121 (no. 19), a = 10.0670(2) Å, b = 10.4687(2) Å, c = 18.4125(3) Å, V = 1940.46(6) Å3, Z = 4. Furthermore, obtained 2,3-dihydrobenzofurans trans diastereoselectivity was established by 1HNMR and X-ray crystallography. All synthesized compounds were subjected to in vitro antioxidant potential (DPPH method). The results revealed that compounds 4e, 4h & 6g possess excellent antioxidant activity, which were superior to the standard antioxidant ascorbic acid. Preliminary structure-activity relationship (SAR) revealed that both the Indole series (4a-k) and thiophene series (6a-k) compounds possess significant antioxidant activity. Chromonyl series (5a-h) of compounds has shown less antioxidant activity. In vitro anticancer activity of selected derivatives screened on three cancer cell lines includes Human breast cancer cell line (MCF-7), Human leukaemia cell line (K-562), Human Cervical Cancer Cell Line HeLa. Among all the evaluated compounds, compound 4e showed potent inhibitory activity with GI50 values below 10 µg/ml on human breast cancer cell line (MCF-7), human cervical cancer cell Line HeLa and GI50 value 37.9 µg/ml on human leukemia cell line (K-562).