Combinatorial synthesis, lead identification, and antitumor study of a chalcone-based positional-scanning library.
A 175-member chalcone library was designed and synthesized from seven differently substituted acetophenones (A(1)-A(7)) and 25 differently substituted aryl or heteroaryl aldehydes (B(1)-B(25)). Potential lead compounds were identified by deconvolution of a two-dimensional library matrix via positional scanning, and the members of the most-active sub-libraries were synthesized and screened against crown-gall tumors with the aid of the potato-disc assay. The resulting hits gave rise to significant antitumor activities, with no antibacterial effect on the tumor-producing bacterium Agrobacterium tumefaciens. Two identified lead structures, (2E)-3-(2-chlorophenyl)-1-phenylprop-2-en-1-one (A(1)B(9)) and the hydroxy analogue (2E)-3-(2-chlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (A(2)B(9)), are promising candidates to be developed into highly effective anticancer chemotherapeutics.
Ullah
Ahsan
A
Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.
Ansari
Farzana Latif
FL
Nazir
Samina
S
Mirza
Bushra
B
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D047188:Chalcones