13 research outputs found
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