A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one
derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia
to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate
TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted
aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido
[3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against
four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer
(CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal
cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were
identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and
MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis
for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line
inhibitors.
Synthesis of 1-[(Aryl)(3-amino-5-oxopyrazolidin-4-ylidene) methyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic Acid Derivatives and Their Breast Anticancer Activity