Pravin S. Bhale

Design, synthesis, characterization and anti-inflammatory evaluation of novel pyrazole amalgamated flavones.

A series of novel pyrazole amalgamated flavones has been designed and synthesized from 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole 6. The structures of regioisomers 6 and 7 were resolved by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were tested for their in vitro COX inhibition and in vivo carrageenan induced hind paw edema in rats and acetic acid induced vascular permeability in mice. Although the compounds have inhibitory profile against both COX-1 and COX-2, some of the compounds are found to be selective against COX-2, supported by inhibition of paw edema and vascular permeability. Docking studies were also carried out to determine the structural features which sway the anti-inflammatory activity of the tested compounds. The keto and phenolic -OH are major factors that are prominently involved in interaction with COX-2 active site.

Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents

In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a-p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI50 <0.1 and 4μM respectively) as good as adriamycin (GI50 <0.1μM). The compounds were also screened against the normal Vero monkey cell line, which showed moderate selectivity against inhibition of cancer cells. The effect of extended conjugation on activity authenticated by comparing activity profile of compound 5a, 5i and 5m with their simple analogues. Among the synthesized compounds, 5i and 5l were found to be active anti-inflammatory agents in addition to having noteworthy antioxidant potential. These results suggest the possible use of these compounds for the design and development of novel anti-breast cancer agents.

Synthesis and pharmacological evaluation of combretastatin-A4 analogs of pyrazoline and pyridine derivatives as anticancer, anti-inflammatory and antioxidant agents

Three category of N1-phenyl pyrazoline (5a–e), N1-phenyl-sulfonyl pyrazoline (6a–e), and pyridine analogs (8a–d) of combretastatin-A4 were synthesized. The structures of compounds were verified by spectroscopic techniques. All the compounds were screened for their anticancer activity against MCF-7 cell line, antioxidant (DPPH, NO, SOR and H2O2), and anti-inflammatory activity while compounds (8a–d) additionally tested against K562 cell line. Compounds 8a and 8b showed substantial anticancer activity against MCF-7 cell line (GI50 = 5.59 and 11.70 µM), although not comparable with adriamycin (GI50 ⩽ 0.1 µM). However, none of the compound was active against the K562 cell line. Nevertheless, compound 8a displayed better cytostatic activity (TGI = 69.2 µM) than the standard drug adriamycin (TGI = 75.8 µM). Most of the compounds 5a, 5b, 5c, 5e, 6a, 6b, 6c, 6d, 6e 8a, and 8b have excellently inhibited all of the free radicals better than standard drug ascorbic acid, whereas compound 5c and 5b demonstrated significant anti-inflammatory activity comparable with diclofenac sodium, a standard anti-inflammatory drug.

Synthesis, Characterization and Evaluation of 1,3-Bisindolyl-2-Propen-1- One Derivatives as Potent Anti-Breast Cancer Agents

School of Chemical Sciences, Solapur University, Solapur 413255, Maharashtra, India; Department of Chemistry, Yeshwantrao Chavan Mahavidyalaya, Tuljapur, Dist-Osmanabad 413601, Maharashtra, India; Department of Chemistry, A.S.P. College, Devrukh, Dist-Ratnagiri 415804, Maharashtra, India; Computational Chemistry Research Lab, Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranageri, Kolhapur 416013, Maharashtra, India

α-Aroylketene Dithioacetal Mediated Synthesis of (E)-3-(benzo[d]thiazol-2-ylamino)-2-(1-methyl-1H-indole-3-carbonyl)-3-(methylthio)acrylonitrile Derivatives and their Biological Evaluation

BACKGROUND The blending of two pharmacophores would generate novel molecular templates that are likely to exhibit interesting biological properties. OBJECTIVE A facile, efficient and high yielding synthesis of (E)-3-(benzo[d]thiazol-2-ylamino)-2-(1-methyl-1Hindole- 3-carbonyl)-3-(methylthio) acrylonitrile derivatives and evaluation of therapeutic potential. METHOD The synthesis of target molecules has been achieved by reacting 2-aminobenzothiazole and substituted 2-(1-methyl-1H-indole-3-carbonyl)-3,3-bis(methylthio)acrylonitrile in the presence of a catalytic amount of sodium hydride in THF. Structural investigations were carried using 1H NMR, 13C NMR, FT-IR, and HRMS data. RESULTS In vitro anti-tumor evaluation of the synthesized compounds against MCF-7 (breast carcinoma) cell line revealed that they possess good anti-tumor activities. Compounds, 4j and 4i demonstrated significant activities against breast carcinoma (GI50 14.3 and 19.5 µM respectively). Most of the synthesized compounds were also found to be excellent NO, H2O2, DPPH, and superoxide radical scavengers. Anti-diabetic and antiinflammatory evaluation also displayed moderate activity. CONCLUSION Among the compounds synthesized some of the compounds possess significant anticancer, antioxidant and anti-inflammatory properties.

Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property.

This study investigates anti‐inflammatory activity with improved pharmacokinetic and non‐ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti‐inflammatory activity with almost non‐ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation‐induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti‐inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non‐ulcerogenic potential of ester prodrugs of ketoprofen.