Synthesis and biological evaluation of asymmetric indole curcumin analogs as potential anti-inflammatory and antioxidant agents.
Abstract A series of asymmetric indole curcumin analogs were synthesized and evaluated as possible inhibiters of pro-inflammatory enzymes such as COX-2, pro-inflammatory cytokines as TNF-α and IL-6, trypsin and β-glucuronidase. They were also tested for antioxidant activities. The results showed that compounds 5e and 5h were found to be the most potent inhibitors of COX-2 (83.33%, 82.50%) and β-glucuronidase (67.80%, 64.12%). All the synthesized compounds exhibited promising activity against IL-6 in a range of 71-100% at 10 µM concentration. Compounds 5f, 5h, 5e, 5c and 5d showed significant inhibition against TNF-α (28-51%) and IL-6 (87-98%) with low toxicity (45-51%) against CCK-8 cells. With few exceptions, all other compounds were found to be good to excellent inhibitors of IL-6 and moderate inhibitors of TNF-α; however, the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 5c, 5b, 5j and 5g were found to possess excellent reducing activity and 5b, 5c and 5h were moderate DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavengers.
Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University , Solapur , India .
Babasaheb P
BP
Bandgar
Santosh N
SN
Kinkar
Hemant V
HV
Chavan
Shivkumar S
SS
Jalde
Rafik U
RU
Shaikh
Rajesh N
RN
Gacche
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D014361:Trypsin Inhibitors; D003474:Curcumin