title: Anti-tumor and proapoptotic effect of novel synthetic benzophenone analogues in Ehrlich ascites tumor cells.
abstract: A series of substituted benzophenone analogues, (2-aroyl-4-methylphenoxy)acetamides 4a-e, have been synthesized via three-step synthesis sequence beginning with the 2-hydroxybenzophenones 1a-e in excellent yield. 1a-e on reaction with ethyl chloroacetate afford ethyl (2-aroyl-4-methylphenoxy)acetates 2a-e which on alkaline hydrolysis afforded (2-aroyl-4-methylphenoxy)ethanoic acid 3a-e. Compounds 3a-e on condensation with p-chloroaniline furnished benzophenone analogues 4a-e. In the present report, we investigated the anti-tumor and proapoptotic effect of benzophenones in Ehrlich ascites tumor (EAT) cells. Treatment of benzophenones in vivo resulted in inhibition of proliferation of EAT cells and ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells is mediated through activation of caspase-3. These results suggest a further possible clinical application of these synthetic compounds as potent anti-tumor and proapoptotic compounds.
authors.affiliation: Department of Studies in Applied Botany and Biotechnology, University of Mysore, Manasagangotri, Mysore 570 006, India.
authors.forename: B T
authors.initials: BT
authors.lastname: Prabhakar
authors.forename: Shaukath Ara
authors.initials: SA
authors.lastname: Khanum
authors.forename: K
authors.initials: K
authors.lastname: Jayashree
authors.forename: Bharathi P
authors.initials: BP
authors.lastname: Salimath
authors.forename: S
authors.initials: S
authors.lastname: Shashikanth
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001577:Benzophenones / Q000737:chemistry / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010718:Phosphatidylserines / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D061945:Caspase Inhibitors; D004273:DNA, Neoplasm; D010718:Phosphatidylserines; D016159:Tumor Suppressor Protein p53; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases