Synthesis of sulpha drug acridine derivatives and their evaluation for anti-inflammatory, analgesic and anticancer activity

Abstract

Various sulpha drugs i.e. sulphaacetamide, sulphathiazole, sulphadiazine and sulphamerazine are coupled with 9-chloro-2,4(un)substituted acridines and 9- isothiocyanato-2, 4(un) substituted acridines to give corresponding coupled products <b>3a-f</b> and <b>4a-h</b> respectively. The structures of all synthesized compounds have been confirmed by spectroscopic methods.

Anti-inflammatory activity evaluation of <b>3a,b,c</b> and <b>4a</b>-<b>h</b> was carried out and compounds <b>4a,</b> <b>4d, 4g</b> and <b>4h</b> showed 8,13,22 and 3% activity respectively at 100mg/<i> </i>kg p.o. Analgesic activity evaluation of <b>3a,b,c</b> and <b>4a-h</b> indicated that these compounds possess 25,75,50,25, 50,50, 0.75, 50, 50 and 50% analgesic activity at 100mg/kg p.o. Anticancer activity

evaluation of <b>3a-f</b> and <b>4a-h</b> against a small panel of seven cancer cell lines consisting of lung (NCIH 460);colon (HT 29): melanoma (LOX); breast (MCF 7 and MCF 7 / ADR); prostate (DU 145) and CNS (U251) tumors was carried out. Best GI₅₀ (concentration which inhibits the cell growth by 50%) values are shown by <b>4b</b>, 0.4 μ<i>M </i>(lung carcinoma, cell line NCIH

460): <b>4b,</b> 0.3 μ<i>M </i>(colon tumor, cell line HT29); <b>3e</b>, 7.2μm (melanoma tumor, cell line LOX): <b>4b</b>, 0.7μ<i>M</i> (breast tumor, cell line MCF7); <b>4c</b>, 1.9μ<i>M</i> (breast tumor, cell line MCF7/ADR); <b>4b</b>, 0.8μ<i>M </i>(prostate tumor, cell line DU 145) and <b>4b</b>, 1.4μ <i>M</i> (CNS tumor, cell line U251) respectively. Out of all the compounds reported here GI₅₀ value shown by <b>4c</b> i.e.

1.9μ<i>M </i>against breast tumor (MCF7/ADR) is quite close to the GI₅₀ value i.e.1.2μ<i>M</i> of the sta ndard drug doxorubicin. Also it is worthwhile to mention here that compound <b>4b</b>, has shown good anticancer activity against four tumor cell lines i.e. GI₅₀ value < 1μ <i>M.</i>