Synthesis and Evaluation of C 2 Arylidene Aryl Congeners of Lantadenes as Anticancer Agents

Abstract

Lantadenes A and B were isolated and various lantadene conjugates were synthesized The structures of lantadenes and derivatives were submitted to Developmental Therapeutics Program National Cancer Institute DTP NCI USA Selected compounds were screened for in vitro cytotoxic potential over NCI 60 human cancer cell lines composite of 9 different type of cancers including leukemia non small cell lung cancer colon cancer CNS cancer melanoma ovarian cancer renal cancer prostate cancer and breast cancer panel Results indicated that mean graph midpoint MG MID value of reduced lantadene A MG MID 569 was higher than standard Cisplatin MG MID 566 while 2 3 Phenylprop 2 en 1 ylidene 22and#946; hydroxyl 3 oxoolean 12 en 28 oic acid MG MID 552 was comparable with Cisplatin NCI s COMPARE molecular mechanistic analysis was performed and it showed that compounds were in significant number of correlations with activity patterns of mechanistic set of compounds PCC and#8805; 060 In the literature no molecular targets have been reported for these target vectors which suggested that anticancer activity of test compounds were might be due to new molecular mechanistic targets Significance of lantadenes and their cinnamoyl and vanillyl integrated congeners were further explored for selective cytotoxicity and molecular mechanistic establishment via NF and#954;B and Akt1 inhibitory expression on A549 cells 2 3 Phenylprop 2 en 1 ylidene 22and#946; hydroxyl 3 oxoolean 12 en 28 oic acid showed significant anti melanoma activity on C57BL 6 mice