Synthesis and biological evaluation of some substituted-2-N-(5-chloro-2-methoxy-4-methylphenylsulphonyl) glutamic acid derivatives against prostate cancer cell line PC3.
New series of substituted glutamine 5a-l and glutamic acid diamides, diureide and dihydrazide 7a-e were synthesized from parent glutamic acid compound 3 and evaluated for their cytotoxic activity against tumor cell line PC3 (prostate cancer cell line). Most of the tested compounds exploited potent growth inhibitory activity with IC(50) values ranging 0.034-3.97 µM. Particularly, compounds 5a, 3, 5j, 5b, 7c, 7e, 5l, and 5k exhibited superior potency (IC(50)=0.034, 0.04, 0.05, 0.074, 0.25, 0.4, 0.49, 0.522 µM, respectively) to the reference drug Doxorubicin (IC(50)=0.63 µM), while compound 7b showed IC(50), 0.71 µM, comparable to that of Doxorubicin. In summary, the newly synthesized compounds provided promising new lead for the future design and development of glutamine and glutamic acid derivatives as novel antitumor agents. The quantitative structure-activity relationship (QSAR) study was applied to find a mathematical correlation between the structures of compounds and their activity against PC3 cell line expressed as IC(50) values.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Ghaneya Sayed
GS
Hassan
Doaa Ezzat
DE
Abdel Rahman
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D018698:Glutamic Acid