الفهرس | Only 14 pages are availabe for public view |
Abstract A variety of steroids with unusual and interesting structures have been synthesized and evaluated for their anti-tumor activity, In this study, the most structurally promising compounds of the novel steroidal heterocyclic derivatives, 7a, 10a, 12b, 18, 22a and 27 were investigated individually as anti-tumor agents against hepatoma (HepG2) cell lines. all tested compounds showed best results when dissolved in olive oil in 50 and 100 µM/ml and at incubation time 72 h. In case of using DMSO as solvent, IC50 of all tested compounds elevated than that obtained in case of olive oil. However compound 27 showed also pronounced inhibition of HepG2 cells when dissolved in DMSO in 50 and 100 µM/ml at incubation time 72 h (IC50 = 40µM). The results revealed that, olive oil is suitable vehicle for anti-tumor drug and is better than DMSO in this respect. Anti-tumor activity was evaluated on EAC bearing mice using animal model. All tested novel steroid derivatives 7a, 10a, 12b, 18, 22a and 27 at dose level of (25mg/kg body weight), completely inhibited the tumor growth in the experimental model and showed zero tumor volume at the end of in vivo experiment, Treatment with all our novel compounds remain the hemoglobin content, body weight, hematocrit % and WBC counts near to normal values and similar to values observed with the most commonly clinically used drug, 5-flurouracil. Furthermore, none of the treated mice with novel compounds exhibited any abnormal behavioral or any toxicity symptoms of dose used during this study. They were active with no loss of appetite and showed no dizziness or erection of hairs or hypothermia. This indicated the relative safety and high activity of all tested compounds at the specified low dose we used. |