TY - JOUR

T1 - Synthesis of thiazole linked chalcones and their pyrimidine analogues as anticancer agents

AU - Kesari, Chekrapani

AU - Rama, Koteshwar Rao

AU - Sedighi, Khwajanezrabodin

AU - Stenvang, Jan

AU - Bjorkling, Fredrik

AU - Kankala, Shravankumar

AU - Thota, Niranjan

PY - 2021

Y1 - 2021

N2 - A series of nine novel thiazole linked chalcones, (E)-3-(4-methyl-2-(4(trifluoromethyl)phenyl)thiazol-5-yl)-1-phenylprop-2-en-1-one derivatives 7-15 were synthesized. To establish the structure-activity relationship (SAR), furthermore, the corresponding, ring-closed pyrimidine analogs 17-23 were synthesized. The derivatives thus obtained were evaluated for their anti-cancer activity against three genetically different colorectal cancer (CRC) cell lines. Thiazole derivatives 7, 9, and10 showed anti-cancer activity with GI50 values ranging from 0.19 to 100 mu M. Importantly, compounds 7 and 10 outperformed the standard drug cisplatin in the tested cell lines and thus show promise for further optimization. Some of pyrimidine derivatives retain activity comparable to cisplatin in the HT-29 cell line, e.g. compounds 17 and 18 with IC50 of 25 mu M, however, none of these compounds demonstrated improved antiproliferative activity as compared with the starting thiazole, thus the enone linker was critical for obtaining more active compounds in this series.

AB - A series of nine novel thiazole linked chalcones, (E)-3-(4-methyl-2-(4(trifluoromethyl)phenyl)thiazol-5-yl)-1-phenylprop-2-en-1-one derivatives 7-15 were synthesized. To establish the structure-activity relationship (SAR), furthermore, the corresponding, ring-closed pyrimidine analogs 17-23 were synthesized. The derivatives thus obtained were evaluated for their anti-cancer activity against three genetically different colorectal cancer (CRC) cell lines. Thiazole derivatives 7, 9, and10 showed anti-cancer activity with GI50 values ranging from 0.19 to 100 mu M. Importantly, compounds 7 and 10 outperformed the standard drug cisplatin in the tested cell lines and thus show promise for further optimization. Some of pyrimidine derivatives retain activity comparable to cisplatin in the HT-29 cell line, e.g. compounds 17 and 18 with IC50 of 25 mu M, however, none of these compounds demonstrated improved antiproliferative activity as compared with the starting thiazole, thus the enone linker was critical for obtaining more active compounds in this series.

KW - Anticancer activity

KW - chalcone derivatives

KW - medicinal chemistry

KW - pyrimidines

KW - thiazoles

U2 - 10.1080/00397911.2021.1884262

DO - 10.1080/00397911.2021.1884262

M3 - Journal article

VL - 51

SP - 1406

EP - 1416

JO - Synthetic Communications

JF - Synthetic Communications

SN - 0039-7911

IS - 9

ER -