Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety. All the benzothiazole derivatives were evaluated for their antidiabetic potential by OGT test followed by assessment of active derivatives on STZ-induced diabetic model. It was observed that nine of twenty novel piperine analogues (5b, 6a-h), showed significantly higher antidiabetic activity in comparison with rosiglitazone (standard). Furthermore, these active derivatives were evaluated for their action as PPAR-γ agonists demonstrating their mechanism of action. The effects on body weight, lipid peroxidation, and hepatotoxicity after administration with active derivatives were also studied to further establish these derivatives as lead molecules for treatment of diabetes with lesser side-effects.

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF-α target. Among all the docked molecules, compound 3f showed best glide score of −6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF-κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver.

Geraniol (GOH), a naturally occurring monoterpene, has been shown to have antiproliferative, cell cycle arrest and apoptosis-inducing effects, and represents a promising cancer chemopreventive agent. In the present study, we investigated the chemopreventive potential of GOH (50 and 100 mg kg⁻¹ body weight) against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated skin tumorigenesis in Swiss albino mice. The topical treatment of GOH, 30 min prior to TPA (2 µg per 200 µl of acetone) treatment significantly inhibited TPA-induced skin edema, hyperplasia, COX-2 induction and oxidative stress response. The GOH treatment also resulted in reduction of TPA-induced ornithine decarboxylase activity and [³H] thymidine incorporation by 53% (P < 0.001) and 41% (P < 0.001), respectively. We found that GOH treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001) and extended the latency period from 4 weeks in DMBA/TPA treatment group to 10 weeks in GOH-pretreated mice. Furthermore, we observed that GOH treatment significantly suppressed the Ras/Raf/ERK1/2 signaling pathway in skin tumor. Consistently, GOH-treated skin tumors showed reduced expression of Bcl-2 and increased expression of Bax in these lesions. Thus, it was concluded that GOH inhibits DMBA/TPA-mediated skin tumorigenesis by attenuating the Ras proliferation pathway and inducing pro-apoptotic state via inhibition of oxidative stress response and inflammation. Copyright © 2012 John Wiley & Sons, Ltd.

A series of 1-(4-methoxyphenyl)-2-[5-{(biphenyl-4-yloxy)methyl}4-(substituted phenyl)-3-mercapto-(4H)-1,2,4-triazol-3-ylthio)] ethanones (6a–6s) and 4-(substituted phenyl)-3-(morpholin/pyrrolidin-4-ylmethylthio)-5-(4-phenylphenoxymethyl)-4H-1,2,4-triazoles (7a–7e) were synthesized in order to obtain new compounds with potent anti-inflammatory and analgesic activity with insignificant ulceration. Among the synthesized compounds, (6c), (6e), (6g) and (6l) from triazole series and (7b) and (7e) from Mannich base series were found to exhibit significant anti-inflammatory activity with 59.69, 59.69, 64.69, 79.84, 54.54, 79.69% and 52.55, 57.50, 72.52, 83.03, 60.06, 84.08% inhibition of paw edema at 3 h and 5 h respectively, in comparison to the standard drug ibuprofen (78.93 and 82.58% at 3 h and 5 h). The active compounds were further tested for their analgesic activity and gastric ulceration study. Compounds 6g, 7b and 7e exhibited significant analgesic activity with reaction time (3.60, 3.22, 3.88 s) respectively at 60 min. without causing any gastric irritation. These compounds were also screened for their in vitro antimicrobial activity, Compounds 6f, 6g, 6h, 6l, 6o, 6p, 7a, 7b and 7c showed significant zone of inhibition against various antimicrobial stains. It is concluded that the compounds 6g, 7b and 7e possess a good spectrum of activities. Compound 7e may be considered potent for development of better anti-inflammatory agent. The antimicrobial activity revealed that most of the compounds showed moderate to significant activity. Compounds containing nitro, chloro, bromo and fluoro group showing better activity. All the compounds from 7a, 7b and 7e were active against gram positive bacteria (S. aureus).