Anticancer thiopyrano[2,3-d][1,3]thiazol-2-ones with norbornane moiety. Synthesis, cytotoxicity, physico-chemical properties, and computational studies

Bioorganic & Medicinal Chemistry
Roman LesykAndrzej Gzella

Abstract

A series of novel 9-substituted-3,7-dithia-5-azatetracyclo[9.2.1.0(2,10).0(4,8)]tetradecen-4(8)-ones-6 have been synthesized by a stereoselective hetero-Diels-Alder reaction of 5-ylidene-4-thioxo-2-thiazolidone derivatives with norbornene-2. All the compounds have been evaluated for antitumor activity in in vitro human tumor cell lines, and 10 of them possessed significant and selective cytotoxicity (MGM logGI50 approximately -4.17 to -4.98, for individual cell lines logGI50 up to -8). COMPARE analyses of differential growth inhibition patterns of compounds at the GI50 level showed high correlations with some of the antitubulin agents. The lipophilicity of the compounds was studied by RP-TLC and found to correlate well with calculated logP values. Docking and structure-activity relationship studies produced seven QSAR models with 2 or 3 variables, with correlation coefficients r2>0.9 and leave-one-out cross-validation correlation coefficients, q2>0.8.

References

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Citations

Feb 3, 2012·Archives of Pharmacal Research·Awwad A RadwanTarek Aboul-Fadl
Dec 21, 2013·European Journal of Medicinal Chemistry·Avinash C TripathiShailendra K Saraf
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Robabeh BaharfarS Mohammad Vahdat
Dec 7, 2011·Scientia pharmaceutica·Danylo KaminskyyRoman Lesyk
Sep 26, 2012·Scientia pharmaceutica·Anna KryshchyshynRoman Lesyk
Jul 3, 2015·Chemical & Pharmaceutical Bulletin·Nadia Hanafy MetwallyDoha Samir Okpy
Aug 16, 2016·European Journal of Medicinal Chemistry·Franco Henrique A LeiteMarcelo Santos Castilho
Apr 5, 2016·Organic & Biomolecular Chemistry·Shanchao WuChunquan Sheng
Jun 16, 2018·Scientia pharmaceutica·Anna KryshchyshynRoman Lesyk
May 29, 2020·Parasitology Research·Flávio Simas Moreira NeriFranco Henrique Andrade Leite
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sergio Hidalgo-FigueroaGabriel Navarrete-Vázquez
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Heejeong ChoiHyung Ryong Moon

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