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Issue 32, 2017
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An efficient one-pot approach for the regio- and diastereoselective synthesis of trans-dihydrofuran derivatives: cytotoxicity and DNA-binding studies

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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 SN2 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. Compounds 1g and 1r 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, compounds 1g and 1r showed significant topoisomerase II inhibitory activities. Moreover, an in silico study of these synthesized compounds revealed that they possess drug-like properties.

Graphical abstract: An efficient one-pot approach for the regio- and diastereoselective synthesis of trans-dihydrofuran derivatives: cytotoxicity and DNA-binding studies

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Publication details

The article was received on 15 Jun 2017, accepted on 25 Jul 2017 and first published on 25 Jul 2017


Article type: Paper
DOI: 10.1039/C7OB01456B
Citation: Org. Biomol. Chem., 2017,15, 6837-6853
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    An efficient one-pot approach for the regio- and diastereoselective synthesis of trans-dihydrofuran derivatives: cytotoxicity and DNA-binding studies

    Y. Tangella, K. L. Manasa, V. Laxma Nayak, M. Sathish, B. Sridhar, A. Alarifi, N. Nagesh and A. Kamal, Org. Biomol. Chem., 2017, 15, 6837
    DOI: 10.1039/C7OB01456B

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