Design, synthesis, biological evaluation and QSAR studies of novel bisepipodophyllotoxins as cytotoxic agents

Bioorganic & Medicinal Chemistry
Ahmed KamalSunanda G Dastidar

Abstract

Two moieties of epipodophyllotoxin have been linked at C4-position to provide novel bisepipodophyllotoxin analogues. These have been evaluated for their anticancer potential and DNA-topoisomerase II poisoning activity. Most of these analogues have exhibited promising in vitro anticancer activity against different human tumour cell lines and interestingly 4(')-O-methylated analogues have shown increased cytotoxic activity. Similarly, the DNA-topo II poisoning activity tested for these compounds has not only exhibited the DNA cleavage potential comparable to etoposide, but for some compounds this cleavage potential is superior to etoposide. Further, an interesting structure-activity relationship of these epipodophyllotoxin dimers have been generated on the basis of GI(50) values. The equations indicated that GI(50) activity is strongly dependent on structural and thermodynamic properties. These QSAR results are discussed in conjunction with conformational analysis from molecular modelling studies. QSAR models developed in these studies will be helpful in the future to design novel potent bispodophyllotoxin analogues by minor structural modifications.

Citations

Nov 8, 2003·Bioorganic & Medicinal Chemistry·Ahmed KamalSunanda G Dastidar
Dec 15, 2007·Nature Reviews. Microbiology·James C SacchettiniJoel S Freundlich
Jul 19, 2013·Journal of Asian Natural Products Research·Jing LiuDa-Jiang Huang
Nov 17, 2012·European Journal of Medicinal Chemistry·Ma Ángeles CastroArturo San Feliciano
May 16, 2014·Medicinal Research Reviews·Ying-Qian LiuKuo-Hsiung Lee

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