Hemant V. Chavan

Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents

A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent.

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, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors

Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 μM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 μM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 μM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.

Design, synthesis, characterization and biological evaluation of novel pyrazole integrated benzophenones

A series of novel pyrazole integrated benzophenones (9a-j) have been designed, synthesized from 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole 6. The structures of the regioisomers 6 and 7 were determined by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds (9a-j) were evaluated for in vivo anti-inflammatory activity by carrageenan paw edema in rats and in vitro COX-1/COX-2 inhibition and antioxidant potential. Among the synthesized compounds, compounds 9b, 9d and 9f, were found to be active anti-inflammatory agents in addition to having potent antioxidant activity.

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 biological evaluation of nitrogen-containing benzophenone analogues as TNF-α and IL-6 inhibitors with antioxidant activity

A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-alpha and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81-89%, 09-42% at 10 and 1 microM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-alpha (54%) and IL-6 (97%), (47%) at 10 and 1 microM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-alpha, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity.

An Efficient Solvent-Free Synthesis of Naphthopyranopyrimidines Using Heteropolyacid as an Ecofriendly Catalyst

An efficient, one-pot, three-component synthesis of naphthopyranopyrimidines using β-naphthol, aldehydes, and 6-amino-1,3-dimethyl uracil catalyzed by heteropolyacid has been achieved within a short period of time. The present methodology offers several advantages such as ecofriendly catalyst, low catalyst loading, short reaction time, simple purification procedure, and excellent yields.

Synthesis and biological evaluation of asymmetric indole curcumin analogs as potential anti-inflammatory and antioxidant agents

Abstract A series of asymmetric indole curcumin analogs were synthesized and evaluated as possible inhibiters of pro-inflammatory enzymes such as COX-2, pro-inflammatory cytokines as TNF-α and IL-6, trypsin and β-glucuronidase. They were also tested for antioxidant activities. The results showed that compounds 5e and 5h were found to be the most potent inhibitors of COX-2 (83.33%, 82.50%) and β-glucuronidase (67.80%, 64.12%). All the synthesized compounds exhibited promising activity against IL-6 in a range of 71–100% at 10 µM concentration. Compounds 5f, 5h, 5e, 5c and 5d showed significant inhibition against TNF-α (28–51%) and IL-6 (87–98%) with low toxicity (45–51%) against CCK-8 cells. With few exceptions, all other compounds were found to be good to excellent inhibitors of IL-6 and moderate inhibitors of TNF-α; however, the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 5c, 5b, 5j and 5g were found to possess excellent reducing activity and 5b, 5c and 5h were moderate DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavengers.

Synthesis and antioxidant, cytotoxicity and antimicrobial activities of novel curcumin mimics

Claisen-Schmidt condensation of 3-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)-2,4,5- trimethoxybenzaldehyde 3 and various aromatic, heterocyclic and alicyclic amides of 3- aminoacetophenone 6(a–s) afforded novel curcumin mimics. All the synthesized compounds were characterized by IR, 1H NMR, Mass spectroscopy and evaluated for antioxidant, cytotoxicity and antimicrobial activity. Out of the 20 compounds screened, compounds 7i, 7l, 7q, and 7n have shown excellent radical scavenging activity, compounds 7o, 7t, 7f, and 7r have shown significant xanthine oxidase inhibition, and compounds 7a, 7k and 7l were found to be potent inhibitors of selected cancer cell lines. Compounds 7h, 7t, 7l, 7i, and 7e have shown good antibacterial activity, whereas compounds 7j, 7f, 7o, 7h, and 7t exhibited significant antifungal activity.

Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents

A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2′-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.