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Microwave-Assisted Synthesis of Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives and Evaluation of their Biological Activity

[ Vol. 18 , Issue. 1 ]

Author(s):

Pallava Nagaraju, Pedavenkatagari Narayana Reddy*, Pannala Padmaja* and Vinod G. Ugale   Pages 49 - 57 ( 9 )

Abstract:


A new class of phenylbenzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and pyrano[ 2,3-d]thiazolo[3,2-a]pyrimidine-5-one derivatives have been synthesized via one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one with various aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2- nitroethenamine under microwave irradiation. This transformation involves the formation of thiazole or benzothiazole fused pyranopyrimidinone ring by the formation of two C-C bonds and one C-O bond in a single synthetic operation. This rapid one-pot reaction does not require a catalyst, it is solvent-free, avoids chromatographic purification, and provides good yields. The synthesized compounds were evaluated for their antiproliferative activity against four cancer cell lines, namely DU 145 (prostate cancer), MDA-MB-231 (breast cancer), Hela (Human cervical cancer), HT-29 (Human colon cancer) and HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal HEK293 cells. Compound 12h exhibited the most potent antiproliferative activity against the tested cell lines, while other test compounds showed weak or moderate antiproliferative activity, among them 12d, 12e and 14d displayed showed IC50 values in the low micromolar range. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

Keywords:

Pyranopyrimidine, thiazolopyrimidine, pyranothiazolopyrimidine, (E)-N-Methyl-1-(methylthio)-2-nitro-ethenamine, antiproliferative activity, molecular docking.

Affiliation:

Department of Chemistry, School of Science, Gitam University, Hyderabad (T.S), 502 329, Department of Chemistry, School of Science, Gitam University, Hyderabad (T.S), 502 329, Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur- 425405, Maharashtra

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