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

Abstract

Various 3,4-diaryl-2-iminothiazolines <b>1a-s</b> 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 (<b>2a-k, n-p</b>) and 3, 4-diaryl-2-imino-N-(2'-pyrazinyliminomethyl)-4-thiazoline (<b>3a-m, q-s</b>) 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 (<b>2o,p</b>) and 3,4-diaryl-2-imino-N-(2'-carbonylpyrazinyl)-4-thiazoline (<b>3q-s</b>) derivatives. The structures of all synthesized compounds have been confirmed by spectroscopic methods. Compounds <b>2a-c,e-h,k,n,p, 3a-i</b> and <b>3l,m,q</b> 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 GI₅₀ values are shown by <b>3f,</b> 11.5 <img src='/image/spc_char/micro.gif' border=0>M (prostate tumor, cell line DU 145), <b>3f,</b> 1.0 <img src='/image/spc_char/micro.gif' border=0>M (colon tumor, cell line HT 29), <b>2n,</b> 6.2<img src='/image/spc_char/micro.gif' border=0>M (breast tumor, cell line MCF 7), <b>2p,</b> 4.8<img src='/image/spc_char/micro.gif' border=0>M (breast tumor, cell line MCF 7/ADR), <b>2p,</b> 6.3<img src='/image/spc_char/micro.gif' border=0>M (CNS tumor, cell line U 251) and <b>3f,</b> 0.9 <img src='/image/spc_char/micro.gif' border=0>M (lung large carcinoma, cell line NCIH 460) respectively. Compound <b>3f</b> has shown good anticancer activity against three cancer cell lines, whereas compounds <b>2n</b> and <b>2p</b> against one and two cancer cell lines respectively. Antiinflammatory activity evaluation of <b>2a-k,n,o,p,</b> <b>3a-m</b> and <b>3q,r,s</b> has been carried out and compounds <b>2a-h, 2j, 2o,p, 3a,b,c,g,m </b>and <b>3r </b>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 100mg/kg p.o. Analgesic activity, evaluation of <b>2a-k,n,o,p, 3a-m </b>and <b>3q,r,s</b> 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 100mg/kg p.o.