Synthesis of biscoupled hemin-thiazoline derivatives and their anticancer activity evaluation

162-167A number of biscoupled hemin-thiazoline derivatives 3a-i have been synthesized and screened in vitro against six human cancer cell lines consisting of lung large (NCIH460), colon (HT29), breast (MCF7 and MCF7/ADR), prostate (DU 145) and CNS (U251) tumors. Compound 3e exhibits good anticancer activity against lung large (NCIH460; GI50 4.3MM), where compound 3g shows good anti cancer activity against colon (HT29; GI50 0.9 μM), breast (MCF7; GI50 0.5μM; MCF7/ADR; GI50 1.8μM), prostate (DU 145; GI50 1.6μM) and CNS (U251; GI50 2.5μM) tumors

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

2659-2666Various 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 3a-f and 4a-h respectively. The structures of all synthesized compounds have been confirmed by spectroscopic methods. Anti-inflammatory activity evaluation of 3a,b,c and 4a-h was carried out and compounds 4a, 4d, 4g and 4h showed 8,13,22 and 3% activity respectively at 100mg/ kg p.o. Analgesic activity evaluation of 3a,b,c and 4a-h 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 3a-f and 4a-h 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 4b, 0.4 μM (lung carcinoma, cell line NCIH 460): 4b, 0.3 μM (colon tumor, cell line HT29); 3e, 7.2μm (melanoma tumor, cell line LOX): 4b, 0.7μM (breast tumor, cell line MCF7); 4c, 1.9μM (breast tumor, cell line MCF7/ADR); 4b, 0.8μM (prostate tumor, cell line DU 145) and 4b, 1.4μ M (CNS tumor, cell line U251) respectively. Out of all the compounds reported here GI50 value shown by 4c i.e. 1.9μM against breast tumor (MCF7/ADR) is quite close to the GI50 value i.e.1.2μM of the sta ndard drug doxorubicin. Also it is worthwhile to mention here that compound 4b, has shown good anticancer activity against four tumor cell lines i.e. GI50 value M.</i

Synthsis of hemin and porphyrin derivatives and their evaluation for anticancer activity

113-119N, Ethylaminoadenosine, histamine, 2-amino-2-thiazoline, 4-aminoantipyrine, sulphathiazole and a number of 3,4-diaryl-2-iminothiazolines are coupled with hemin to give bis coupled products 3a, 3b, 3c, 3d, 3e and 3f-m, respectively. Mono coupling of 2-amino-2-thiazoline with hemin gives isomeric mixture of mono coupled product 4. Deuteroporphyrin IX dicarboxylic acid is coupled with 2-amino-2-thiazoline to give bis coupled product 6 which on treatment with MnCl2,4H2O gives compound 7. Compounds 3a-m and 4 have been screened for anticancer activity against a small panel of six cancer cell lines consisting of prostate tumour (DU 145, PC3), colon carcinoma (HT29 or SW620), melanoma (SK-MEL-5, LOX), breast cancer (MCF 7 and adriamycin resistant MCF 7), CNS (U251) and ovarian cancer (IGROV1). Best GI50 (concentration which inhibits the cell growth by 50%), values are shown by 3f, 6.3μM (prostate tumour, cell line DU 145); 3f, 6.1 μM (colon tumor, cell line HT29); 4, 2.09 μM (colon tumor, cell line SW620); 3f, 2.2 μM (melanoma tumor, cell line LOX); 3i, 4.4μM (breast tumor, cell line MCF7/ADR); 3j, 2.68μM (ovarian tumor, cell line IGROV1) and 3g, 1.25μM (CNS tumor, cell line U 251) respectively

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

387-399Various 3,4-diaryl-2-iminothiazolines 1a-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 3l,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 GI50 values are shown by 3f, 11.5 M (prostate tumor, cell line DU 145), 3f, 1.0 M (colon tumor, cell line HT 29), 2n, 6.2M (breast tumor, cell line MCF 7), 2p, 4.8M (breast tumor, cell line MCF 7/ADR), 2p, 6.3M (CNS tumor, cell line U 251) and 3f, 0.9 M (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 100mg/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 100mg/kg p.o

Proline ureas: Synthesis and pharmacological evaluation as VLA-4 antagonists

2004-2020VLA-4 has been identified as a relatively new target for the development of “non-steroidal” alternatives for the treatment of asthma and related respiratory inflammatory diseases. In continuation of search to identify potent VLA-4 antagonists, a series of novel proline urea derivatives have been synthesized. The newly synthesized compounds are evaluated as potential VLA-4 antagonists in vitro and are found to exhibit moderate VLA-4 inhibitory activity

Development of cell death-based method for the selectivity screening of caspase-1 inhibitors

Caspase-1 selective inhibitors are novel therapeutic agents for inflammatory diseases. Selectivity assays for caspases can be initiated with purified enzyme, making these assays very costly and time consuming. Therefore, there is a need to develop a fast and reliable cell-based assay, which can be used for the selectivity screening of multiple caspases in a biologically relevant context in a single assay. In this study, we have developed an assay in which DNA fragmentation, a hallmark of apoptosis, of Jurkat cell line was examined post induction with etoposide in the presence or absence of inhibitors of caspases 1, 3, 8, 9 and pan-caspase inhibitors. We observed that caspases-3, -8, -9 and pan caspase inhibitors resulted in significant inhibition of etoposide-induced DNA fragmentation. However, caspase-1 specific inhibitor failed to prevent DNA fragmentation, suggesting that either caspases belonging to caspase-1 family (1, 4 and 5) are not present in the Jurkat cells or might not be involved in the etoposide-induced DNA fragmentation. Since the inhibition of caspases 3, 8 and 9 is accompanied by the down regulation of the activity of a cascade of caspases (caspases 2, 6, 7, 9 and 10), selectivity of caspase-I inhibitors can be ascertained for the above panel (caspases 2, 6, 7, 8, 9 and 10) of caspases from this single assay