Mohammad Sarwar Alam

Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis-heterocycles: Their anti-inflammatory and anti-nociceptive activities

A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration.

Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis

The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects. Skin tumors were initiated by applying 160u2009nmol DMBA and promoted by twice weekly applications of 8.5u2009nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However, in mice pretreated with 30u2009µL eugenol, no tumors were detected until 8 wk (following anti‐initiation protocol) and until 14 wk (following antipromotion protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively. The effect of eugenol was assessed on specific stages of carcinogenesis. Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21WAF1 levels in epidermal cells indicating induction of damage to the DNA. However, pretreatment with eugenol led to overexpression of these genes, which probably helped stimulate apoptosis of the initiated cells. To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol, its effect was investigated on markers of tumor promotion and inflammation: ODC activity and iNOS and COX‐2 expression, and on levels of proinflammatory cytokines (IL‐6, TNF‐α, and PGE2). Eugenol markedly inhibited all. Eugenol also inhibited the upstream signaling molecule: NF‐κB, which regulates the expression of these genes. TPA‐induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol. From these results, it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative, anti‐inflammatory, and antioxidant activities.

Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents

A series of benzfused heterocyclic derivatives such as amide conjugates of 2-(benzo[d]thiazol-2-ylthio)acetic acid with aromatic/aliphatic/cyclic secondary amines (5a-5o & 8a-8m); 1,2,3-triazole conjugates of 2-mercaptobenzothiazoles and amide conjugates of indole-3-glyoxalic acid with cyclic secondary amines (14a-14g) have been synthesized and were screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth microdilution assay method. Compounds 8b, 8f, 8g and 8l inhibited the growth of the H37Rv strain at concentrations of 8 μg/mL. These compounds (8b, 8f, 8g and 8l) have been further identified as bactericidal and are completely killing the microbes at 32-64 μg/mL concentrations. Molecular docking studies of the active compounds reveal that these compounds are targeting DprE1 and may act as DprE1 inhibitors.

Chemopreventive effect of farnesol on DMBA/TPA-induced skin tumorigenesis: involvement of inflammation, Ras-ERK pathway and apoptosis.

AIMSnNaturally-derived farnesol has been reported for its chemopreventive and chemotherapeutic efficacy in various cancers. However, the mechanism of action of farnesol is still to be elucidated. The present study demonstrates the chemopreventive potential of farnesol on 9,10-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumorigenesis in Swiss albino mice.nnnMAIN METHODSnFarnesol at three different doses 25, 50 and 100 mg/kg body weight was topically applied to the mouse skin, 30 min prior to TPA (2 microg/200 microl acetone) to evaluate edema, hyperplasia, expression of cyclooxygenase-2 (COX-2), oxidative stress response and hyperproliferation, and expression of Ras, Raf, p-ERK1/2, Bax and Bcl-2 in DMBA/TPA-induced tumors.nnnKEY FINDINGSnFarnesol at both the low doses significantly reduced the TPA-induced skin edema, hyperplasia, expression of COX-2 and oxidative stress response. Interestingly, higher dose of farnesol did not show any significant response. Pretreatment of farnesol significantly decreased TPA-induced ornithine decarboxylase (ODC) activity and [(3)H]thymidine incorporation in dose-dependent manner. During promotion phase, farnesol with higher dose significantly regressed tumor incidence and tumor burden with an extension of latency period of 4-8 weeks. More importantly, low doses of farnesol significantly inhibited Ras/Raf/ERK1/2 signaling pathway in mouse skin tumors whereas higher dose of farnesol induced the pathway. Moreover, farnesol at all doses altered Bax/Bcl-2 ratio which leads to induction of apoptosis as confirmed by DNA fragmentation.nnnSIGNIFICANCEnThese findings revealed that oxidative stress, inflammation, Ras/Raf/ERK1/2 pathway and apoptosis collectively played a crucial role in the chemopreventive activity of farnesol to inhibit the murine skin tumorigenesis.

Trapa natans L. root extract suppresses hyperglycemic and hepatotoxic effects in STZ-induced diabetic rat model.

ETHNOPHARMACOLOGICAL RELEVANCEnTrapa natans L. has a folkloric reputation as nutrient, appetizer and astringent. Its utility as antidiabetic, anticancer, diuretic, aphrodisiac, antidiarrhoeal and in many other maladies is well reported in the literature. Therefore, the present study has been carried out to study the antihyperglycemic effect of root extract of Trapa natans L. and its various fractions. Furthermore, hepatotoxic effects and lipid peroxidation risks have also been evaluated.nnnMETHODSnThe ethanol extract and its successive fractions obtained from roots of Trapa natans have been administered in sucrose loaded and STZ- induced diabetic Wistar rats at doses of 50, 100 and 200mg/kg b.w. Glibenclamide was used as positive control. The evaluation of protective effects of extract as well as fractions against hepatotoxicity and lipid peroxidation at 600mg/kg b.w. has also been carried out.nnnRESULTSnThe methanol fraction emerged as the most potent antihyperglycemic fraction. It has also been found that the ethanolic extract as well as its fractions did not cause any lipid peroxidation and hepatotoxicity risks.nnnCONCLUSIONnIt can be concluded that the intense investigations of the methanol fraction obtained from Trapa natans root extract can be done to provide an alternative natural therapy for hyperglycemia.

Recent trends in electrospinning of polymer nanofibers and their applications in ultra thin layer chromatography

Fabrication of polymer derived electrospun nanofibers by electrospinning as chromatographic sorbent bed for ultra-thin layer chromatography (UTLC) is a very demanding topic in analytical chemistry. This review presents an overview of recent development in the fabrication of polymer derived electrospun nanofibers and their applications to design UTLC plates as stationary phases for on-plate identification and separation of analytes from their mixture solutions. It has been reported that electrospun fiber based stationary phases in UTLC have enhanced separation efficiency to provide separation of analyte mixture in a shorter development time than those of traditional particle-based TLC stationary phases. In addition, electrospun UTLC is cost effective and can be modified for obtaining different surface selectivities by changing the polymer materials to electrospun devices. Electrospun UTLC plates are not available commercially till date and efforts are being rendered for their commercialization. The morphology and diameter of electrospun nanofibers are highly dependent on several parameters such as type of polymer, polymer molecular weight, solvent, viscosity, conductivity, surface tension, applied voltage, collector distance and flow rate of the polymer solution during electrospinning process. Among the aforementioned parameters, solution viscosity is an important parameter which is mainly influenced by polymer concentration. This review provides evidence for the fabrication of UTLC plates containing electrospun polymer nanofibers. Furthermore, the future prospects related to electrospinning and its application in obtaining of different types of electrospun nanofibers are discussed. The present communication is aimed to review the work which appeared during 2009-2014 on the application of polymer derived electrospun nanofibers in ultra thin layer chromatography.

Synthesis of some new s-alkylated 1,2,4-triazoles, their mannich bases and their biological activities.

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 3u2009h and 5u2009h respectively, in comparison to the standard drug ibuprofen (78.93 and 82.58% at 3u2009h and 5u2009h). 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, 3.88u2009s) respectively at 60u2009min. 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).

Ameliorative effects of Trichosanthes dioica Extract in suppressing inflammatory mediators and attenuating oxidative stress.

The present study aimed to investigate the anti-inflammatory activity of the ethanolic extract of the aerial parts of Trichosanthes dioica and its successive fractions. The effect on oxidative stress involved in the pathogenesis of inflammation was evaluated. The ethanolic extract and its successive fractions were administered at a dose of 150 and 300 mg/kg b.u200aw. for testing their anti-inflammatory activity by a carrageenan-induced edema model. The results showed that the ethyl acetate fraction exhibited significant potency against inflammation. Pertaining to mechanistic insight, the anti-inflammatory effect might be attributed to the attenuation in tumor necrosis factor-α level (ELISA assay) and reduced expression of cyclooxygenase-2 and nuclear transcription factor-κB (immunohistochemistry). The alleviation in oxidative stress has been pertinent to the elevation in the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione) by active fractions. Furthermore, the ulcerogenic effect was insignificant even at a three times higher dose. Finally, it was concluded that the ethyl acetate fraction which showed significant biological potential against inflammation and oxidative stress could be viewed as a source of effective treatment.