Design and Synthesis of Curcumin-Like Diarylpentanoid Analogues as Potential Anticancer Agents.
BACKGROUND
Curcumin is a polyphenolic natural compound with multiple targets that used for the prophylaxis and treatment of some type of cancers like cervical and pancreatic cancers. Some recent patent for curcumin for cancer has also been reviewed.


OBJECTIVE
In this study, ten new curcumin derivatives were designed and synthesized and their cytostatic activity evaluated against the Hela and Panc cell lines that some of them showed more activity than curcumin.


METHODS
In the present study, a series of mono-carbonyl derivatives of curcumin were designed and prepared. The details of the synthesis and chemical characterization of the synthesized compounds are described. The cytostatic activities of the designed compounds are assessed in two different tumor cell lines using MTT test.


RESULTS
In vitro screening for human cervix carcinoma cell lines (Hela) and pancreatic cell lines (Panc-1) at 24 and 48 hour showed that all the analogs possessed good activity against these tumor cell lines and compounds 5a, 5c and 6 with high potency can be used as a new lead compounds for the designing and finding new and potent cytostatic agents. Docking studies indicated that compound 5c readily binds the active site of human glyoxalase I protein via two strong hydrogen bonds engaging residues of Glu-99 and Lys-156.


CONCLUSIONS
Our results are useful in guiding a design of optimized ligands with improved pharmacokinetic properties and increased of anti-cancer activity vs. the prototype curcumin compound.
Elahe
E
Qudjani
Maryam
M
Iman
Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran, Tehran, 19419, Iran. adavood@iaups.ac.ir.
Asghar
A
Davood
Mahdi F
MF
Ramandi
Abbas
A
Shafiee
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D017076:Computer-Aided Design; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase; D003474:Curcumin