Sham M. Sondhi

Anticancer, Anti-inflammatory and Analgesic Activity Evaluation of Heterocyclic Compounds Synthesized by the Reaction of 4-Isothiocyanato-4-methylpentan-2-one with Substituted o-Phenylenediamines, o-Diaminopyridine and (Un)Substituted o

4,5-Dimethyl-1,2-phenylenediamine and 4-chloro-1,2-phenylenediamine react with 4-isothiocyanato-4-methylpentan-2-one (15) to give compounds (3a) and (3b), respectively. 3,4-Diaminobenzoic acid reacts similarly with (15) to give a mixture of compounds, possibly (2a) and (2b), which could be cyclized at pH ~5 to compound (3c). 3,4-Diaminopyridine reacted with (15) in DMF to give compounds (5) and (6), whereas condensation of 5,6-diaminopyrimidine and 4,5,6-triaminopyrimidine sulfate under similar conditions gave compounds (8a) and (8b), respectively. Compounds (8a) and (8b) at pH ~4 gave a mixture of compounds (9a), (10a) and (9b), (10b), respectively. Condensation of 4,5-diamino-6-hydroxy-2-mercaptopyrimidine, 4,5-diamino-2,6-dimercapto-pyrimidine and 5,6-diamino-1,3-dimethyluracil hydrate with (15) gave corresponding mercaptopyrimidines (12a), (12b) and (14), respectively. The evaluation of (3a–c), (8a,b), (12a,b) and (14) aganist a small panel of six cancer cell lines, consisting of prostate (DU145), colon (HT29), melanoma (LOX), breast (MCF, MCF7/ADR), ovarian (OVCAR3) and CNS (U251) is reported. The most active was compound (8b), against colon (HT29) (44.2 M). Anti-inflammatory and analgesic activity is also reported.

Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines.

(UN) substituted o-phenylenediamines 1a-g reacted with 3-isothiocyanatobutanal to give pyrimidobenzimidazole derivatives, 2a-g, respectively. Products 4, 6 and 8, 10 were obtained by condensation of 3-isothiocyanatobutanal with 2,3-diaminopyridine, 1,4-diaminobutane and 3-isothiocyanatopropanal with 4,5-dimethyl-1,2-phenylenediamine, o-nitroaniline, respectively. S-Methylation of 2f and 11b gave products 12a and 12b, respectively. Anti-inflammatory and analgesic activity evaluations of 2a-g and 12b were carried out at 50 mg kg(-1) p.o. Compound 2c exhibited good anti-inflammatory (46%) and mild analgesic activity (50%). Antiamoebic activity evaluations (using microdilution method) of 2a-g against Entamoeba-histolytica (strain HM1: IMSS) were carried out and compounds 2a, 2b, 2d and 2g exhibited good antiamoebic activity in vitro.

Synthesis, anti-inflammatory and anticancer activity evaluation of some novel acridine derivatives

Condensation of 9-chloro-2,4-(un)substituted acridines (1a-c) with various amines (2a-e) and 9-isothiocyanato-2,4-(un)substituted acridines (4a,b) with different amines (2a,b,d,e) gave condensed products 3a-o and 5a-g respectively. Compounds 3a-o and 5a-g were screened for anti-inflammatory activity at a dose of 50mg/kg p.o. Compound 3e exhibited 41.17% anti-inflammatory activity which is better than most commonly used standard drug ibuprofen which showed 39% anti-inflammatory (at 50mg/kg p.o.) activity. Anticancer activity evaluation of compounds 3a-o and 5a-g was carried out against a small panel of human cancer cell lines and compounds 3g, 3m and 5g exhibited good anticancer activity against breast (MCF-7), liver (HEP-2), colon (COLO-205, 502713, HCT-15), lung (A-549) and neuroblastoma (IMR-32) cancer cell lines at a concentration of 1 x 10(-5)M.

Solvent free synthesis, anti-inflammatory and anticancer activity evaluation of tricyclic and tetracyclic benzimidazole derivatives.

Heterocyclic benzimidazole derivatives 3a-h, 5a-c and 7a-d have been synthesized by condensation of succinic acid (1) homophthalic acid (4) and 2,3-pyrazinedicarboxlic acid (6) with various substituted diamines under microwave irradiation in good yields. Structures assigned to 3a-h, 5a-c and 7a-d are fully supported by spectral data. All these compounds were screened for anti-inflammatory and anticancer activities. At a dose of 50 mg/kg p.o. compounds 3b (39.4%) and 3c (39.2%) exhibited anti-inflammatory activity, comparable to standard ibuprofen which showed 39% activity at 50 mg/kg p.o. and compound 7c exhibit good anticancer activity against ovary (IGR-OV-1), breast (MCF-7) and CNS(SF-295) human cancer cell lines.

Heterocyclic compounds as inflammation inhibitors.

Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with significant toxicity particularly in the gastrointestinal tract and kidney. Various approaches such as formulation co-administration (of agents to protect the stomach), chemical manipulation and synthesis of new safer anti-inflammatory drugs reported in the literature to overcome the toxicity of NSAIDs have been summarized. As far as synthesis of new more effective and safer anti-inflammatory drugs is concerned, we have reported recent findings in the area of synthesis of heterocyclic compounds such as pyrimidines, imidazole, benzimidazole, thiazole, thiazolidine, acridine, thiourea, alkanoic acid derivatives and other related heterocyclic compounds and their role as inflammation inhibitors.

Microwave-assisted synthesis of N-substituted cyclic imides and their evaluation for anticancer and anti-inflammatory activities

A number of N-substituted cyclic imides 3a-e, 5a-e, 7a-d, and 9a-e have been synthesized in very high yields, by condensation of various diacids 2, 4, 6, and 8 with different amines under microwave irradiation. These compounds were screened for anticancer and anti-inflammatory activities, and compounds 3c, 3e, 5c, 9c, and 9d exhibited anticancer activity against colon (COLO 205) cancer better than 5-fluorouracil and mitomycin-C, and compound 9b exhibited anti-inflammatory activity better than standard drug phenyl butazone.

Synthesis and Anticancer, Antiinflammatory,and Analgesic Activity Evaluation of Some Sulfa Drug and Acridine Derivatives

Summary. Various sulfa drugs were condensed with 4-isothiocyanato-4-methyl-2-pentanone at pH∼3–5 by refluxing in methanol to give various substituted mercaptopyrimidines. On condensation with 9-chloro-2-substituted or -unsubstituted acridines, sulfathiazole gave the corresponding condensed products. N-Ethylaminoadenosine reacted with 9-chloroacridine to the coupled product. Condensation of sulfathiazole with 9-isothiocyanato-2,4-substituted or -unsubstituted acridines afforded the corresponding condensed compounds. The structures of all synthesized compounds were confirmed by spectroscopic methods. Anticancer, antiinflammatory, and analgesic activities of all compounds were investigated.

Synthesis of amidine and amide derivatives and their evaluation for anti-inflammatory and analgesic activities.

A number of amidine derivatives (2a-i) have been synthesized by condensation of 2-cyanopyridine with various 3,4-diaryl-2-imino-4-thiazolines. Various amide derivatives (3a-h) were synthesized by condensation of orotic acid and hydantoin-5-acetic acid with a number of 3,4-diaryl-2-imino-4-thiazolines using microwave irradiation. All the compounds i.e. (2a-i) and (3a-h) synthesized were characterized by spectroscopic means and elemental analysis. Compounds (2a-i) and (3a-h) at 50 mg/kg p.o. were screened for anti-inflammatory activity whereas 2a-d, f, g, i and 3a, b, d, f at 50 mg/kg p.o. were evaluated for analgesic activity. Compounds 2e and 3g exhibited good anti-inflammatory activity (49% and 34%, respectively) and 2f, g showed interesting (50% in each case) analgesic activity.

Antiinflammatory, analgesic and kinase inhibition activities of some acridine derivatives

Abstract9-Chloro-2,4-(un)substituted acridines (1) on condensation with sulpha- diazine, sulphathiazole, and sulphaacetamide gave condensation products 3a-h. 3-Aryl-4-phenyl-2-imino-4-thiazolines (4) on condensation with 9-chloro-2,4-(un)substituted acridines (1) gave condensation products 5a–5o. Both 3a–3h and 5a–5o were purified by crystallization or by chromatography. Structures assigned to 3a–3h and 5a–5o are supported by correct spectral data. Antiinflammatory and analgesic activity screening of 3a, 3e, 3f and 5a–5c, 5e, 5g, 5i, 5m, 5n were carried out using carrageenin induced paw oedema and phenyl quinone writhing assay. Some of the compounds exhibited interesting antiinflammatory or analgesic activities.

Extraction and spectrophotometric determination of Pd(II) with 3,4,4a,5-tetrahydro-3,3,4a-trimethyl-7-(substituted)-pyrimido(1,6-a)-benzimidazole-1-thiol (PBT)

A method for the extraction-spectrophotometric determination of palladium with 3,4,4a,5-tetrahydro-3,3,4a-trimethyl-7-(substituted)-pyrimido(1,6-a)benzimidazole-1-thiol (PBT) is described. PBT-Pd(II) complex is extracted from an acidic aqueous solution (0.01-0.5M HClO(4)) into a chloroform layer. The absorbance is measured at 438 nm and the molar absorptivity found to be 1.033 x 10(4)M(-1) cm(-1). The complex system conforms to Beers law over the range 1.9-28.5 mug/ml palladium(II). The effects of pH (2-6), HClO(4) concentration, PBT concentration and shaking time were studied. The ratio of metal ion to ligand molecules in the coloured complex was found to be 1:4. The tolerance limit for many metals have been determined. Finally, the method has been applied successfully to the determination of palladium in synthetic mixtures and in the standard palladium carbon powder (palladium catalyst).