Synthesis and biological evaluation of nitrogen-containing benzophenone analogues as TNF-alpha and IL-6 inhibitors with antioxidant activity.

Research paper by Babasaheb P BP Bandgar, Sachin A SA Patil, Jalinder V JV Totre, Balaji L BL Korbad, Rajesh N RN Gacche, Baliram S BS Hote, Shivkumar S SS Jalde, Hemant V HV Chavan

Indexed on: 09 Mar '10Published on: 09 Mar '10Published in: Bioorganic & Medicinal Chemistry Letters


A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-alpha and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81-89%, 09-42% at 10 and 1 microM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-alpha (54%) and IL-6 (97%), (47%) at 10 and 1 microM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-alpha, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity.