An efficient one-pot approach for the regio- and diastereoselective synthesis of trans-dihydrofuran derivatives: cytotoxicity and DNA-binding studies. Issue 32 (7th August 2017)

• Record Type: Journal Article
• Authors: Tangella, Yellaiah; Manasa, Kesari Lakshmi; Laxma Nayak, V.; Sathish, Manda; Sridhar, B.; Alarifi, Abdullah; Nagesh, Narayana; Kamal, Ahmed
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 32(2017)
• Page Start: 6837
• Page End: 6853
• Publication Date: 2017-08-07
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob01456b
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A facile one-pot, three component strategy has been developed for the construction of trans -2, 3-dihydrofuran derivatives. All the synthesized compounds have been evaluated for their cytotoxic activity. Abstract : An operationally facile and high yielding one-pot, three-component protocol has been developed for the preparation of selectively trans -2, 3-dihydrofuro[3, 2- c ]coumarins and trans -1, 2-dihydrobenzo[ h ]furo[3, 2- c ]quinolinones. This protocol proceeds through a domino Knoevenagel condensation, a Michael addition followed by intramolecular SN 2 cyclisation. All the synthesized compounds have been evaluated for their in vitro cytotoxic activity against selected human cancer cell lines. Interestingly, most of the compounds have exhibited considerable cytotoxicity with IC50 values <10 μM in all the tested cell lines. Moreover, these compounds showed higher activity against MCF-7 (breast cancer) cell lines compared to other tested cell lines. Compounds1g and1r displayed significant cytotoxicity against all four tested cell lines. Cytotoxicity studies indicated that the toxicity of the synthesized compounds was considerably higher in tumor cells compared to normal cells. The structure–activity relationship studies revealed that the activating groups in these compounds preferably improved the activity compared to the deactivating groups. For a better understanding of the mechanism of action of these compounds, we performed the binding studies with calf thymus DNA (CT-DNA). Both molecular docking studies as well as biophysical studies indicate that these compounds may possess DNA binding affinity through intercalation. Through photocleavage studies, it is evident that they have the potential to cleave pBR322 plasmid DNA strands in a concentration and time dependent manner. In addition, compounds1g and1r showed significant topoisomerase II inhibitory activities. Moreover, an in silico study of these synthesized compounds revealed that they possess drug-like properties.