Synthesis,hydrolysis over silica column,anticancer,anti-inflammatory and analgesic activity evaluation of some pyridine and pyrazine derivatives

摘要

Various 3,4-diaryl-2-iminothiazolines la-s have been condensed with 4-cyanopyridine and 2-cyanopyrazine by refluxing in methanol for about 16 hr to give corresponding 3,4-diaryl-2-imino-N-(4'-pyridyliminomethyl)-4-thiazoline (2a-k,n-p) and 3,4-diaryl-2-imino-N-(2'-pyrazinyliminomethyl)-4-thiazoline (3a-m,q-s) derivatives.In some cases when these pyridyl and pyrazinyl derivatives are purified by column chromatography over silica gel these compounds get hydrolysed to give corresponding 3,4-diaryl-2-imino-N-(4'-carbonylpyridyl)-4-thiazoline (2o,p) and 3,4-diaryl-2-imino-N-(2'-carbonylpyrazinyl)-4-thiazoline (3q-s) derivatives.The structures of all synthesized compounds have been confirmed by spectroscopic methods.Compounds 2a-c,e-h,k,n,p,3a-i and 3I,m,q are screened for anticancer activity against a small panel of six human cancer cell lines consisting of prostate (DU 145) colon (HT 29) breast (MCF 7) breast (MCF 7/ADR),CNS (U 251) and lung large (NCIH 460) tumors.Best GI_(50) values are shown by 3f,11.5 muM (prostate tumor,cell line DU 145),3f,1.0 muM (colon tumor,cell line HT 29),2n,6.2muM (breast tumor,cell line MCF 7),2p,4.8muM (breast tumor,cell line MCF 7/ADR),2p,6.3muM (CNS tumor,cell line U 251) and 3f,0.9 muM (lung large carcinoma,cell line NCIH 460) respectively.Compound 3f has shown good anticancer activity against three cancer cell lines,whereas compounds 2n and 2p against one and two cancer cell lines respectively.Antiinflammatory activity evaluation of 2a-k,n,o,p,3a-m and 3q,r,s has been carried out and compounds 2a-h,2j,2o,p,3a,b,c,g,m and 3r showed 13,32.5,48.8,6.5,13.9,7.0,4.3,16.6,20.0,17.3,27.7,16.2,18.4,34.7,15.6,24.0 and 4.7% activity,respectively,at l00mg/kg p.o.Analgesic activity,evaluation of 2a-k,n,o,p,3a-m and 3q,r,s indicates that these compounds possess 50,25,75,25,50,75,50,50,25,0.0,50,50,0.0,75,50,25,25,25,75,0.0,25,25,25,50,50,75,25,50,75 and 50% analgesic activity at l00mg/kg p.o.