Synthesis and anti breast cancer activity of biphenyl based chalcones.
A series of (2E,2'E)-1,1'-(3-hydroxy-5-methylbiphenyl-2,6-diyl)-bis(3-pheylprop-2-ene-1-ones (5-33) were prepared by the reaction of 1,3-diacetyl biphenyls (1-4) with different aldehydes in presence of catalytic amount of solid KOH in ethanol in excellent yields. The compounds were evaluated for anticancer activity against human breast cancer MCF-7 (estrogen responsive proliferative breast cancer model) and MDA-MB-231 (estrogen independent aggressive breast cancer model) cell lines, HeLa (cervical cancer) cell line, and human embryonic kidney (HEK-293) cells. Most of the compounds preferentially inhibited the growth of the aggressive human breast cancer cell lines, MDA-MB-231 in the range of 4.4-30 μM. The two compounds 9 and 29 proved to be better anticancer agents than the standard drug tamoxifen against the MDA-MB-231 cell lines. Mode of action of these compounds was established to be apoptosis, cell cycle arrest and loss of mitochondrial membrane potential.
Sharma
Anindra
A
Medicinal and Process Chemistry Division, Central Drug Research Institute (CSIR), Lucknow 226001, India.
Chakravarti
Bandana
B
Gupt
Munna Prasad
MP
Siddiqui
Jawed A
JA
Konwar
Rituraj
R
Tripathi
Rama P
RP
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D005260:Female; D006801:Humans
D000475:Alkenes; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D047188:Chalcones; C559238:(2E,2'E)-1,1'-(3-hydroxy-5-methylbiphenyl-2,6-diyl)bis(3-(3-chlorophenyl)prop-2-en-1-one); C559237:(2E,2'E)-1,1'-(4'-chloro-3-hydroxy-5-methylbiphenyl-2,6-diyl)bis(3-phenylprop-2-en-1-one); C010574:biphenyl