Varadaraj G Bhat

Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats

ETHNOPHARMACOLOGICAL RELEVANCE The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders. AIM OF THE STUDY To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. MATERIALS AND METHODS Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats. RESULTS Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10μM) or ODQ (10 μM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10μM) and atropine (1 μM) partially blocked the relaxation, whereas glibenclamide (10 μM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6±6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract. CONCLUSIONS These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.

Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study

Biginelli dihydropyrimidinone derivatives as structural analogs of monastrol, a known human kinesin Eg5 inhibitor, were synthesized. IC50 values of the synthesized compounds against the proliferation of human hepatocellular carcinoma and human epithelial carcinoma cell lines were determined through MTT assay. Molecular docking study gave a clear insight into the structural activity relationship of the compounds in comparison with monastrol.

Insights on the Antioxidant Potential of 1, 2, 4-Triazoles: Synthesis, Screening & QSAR Studies

The aligned manuscript reports synthesis, screening and QSAR analysis of twenty six 1, 2, 4-triazole analogues from their respective aromatic carboxylic acids. The structures of synthesized analogues were characterized using physical and spectral analysis. 1, 2, 4-Triazole analogs antioxidant capacity was determined using DPPH radical scavenging assay. Results revealed that out of L, T & VRT series, VRT series of 1, 2, 4-triazoles have significant antioxidant activities when compared with standard ascorbic acid. To obtain structural insights for development of new antioxidants a 2D-QSAR analysis of this dataset of 26 molecules was performed. The 2D-QSAR models correlate with the in vitro results and explain the salient structural features predominant in the molecules responsible for antioxidant activity.

Honey bee sting and venom offering active as well as passive immunization could reduce swine flu pandemic A (H1N1).

ommended, the prognosis of patients with GBM still remains poor. The median survival after combined therapy is only 14.6 months [1]. Intracranial infection is a lethal post-operative complication of the patients underwent craniotomy for GBM. As the results of unrestrained proliferation and autolysis of bacterium, a large quantity of pro-inflammatory components was released into the cerebrospinal fluid, and which induced an excessive inflammatory reaction, caused severe damage of the brain, thus largely accounting for the unfavourable outcome of meningitis. Besides that damage, the patients with meningitis often suffer from high fever, vomiting, conscious disturbance, so the post-operative chemotherapy and radiotherapy often cannot be performed in time. However, we observed that the patients who suffered this potentially lethal post-operative complication could potentially acquire a longer survival time comparing with those without post-operative meningitis. But the similar survival improvement cannot be observed in the patients suffering from other less severe complications, such as wound infection, leakage of CSF. Moreover, analogous manifestation has been reported in other malignancies besides GBM [2]. Therefore, we hypothesize that post-operative meningitis might prolong the survival time of patients with GBM. Previous studies have demonstrated that immunosuppressive cytokines such as transforming growth factor b and interleukin 10 elaborated by GBM could down-regulate the function of T-cell and macrophage which infiltrated the GBM. So the two kinds of cell could not produce pro-inflammatory cytokines and thus could not initiate the immune responses. When post-operative intracranial infection occurred, the space of tumor was replaced by infiltration of inflammatory cells, so the secretion and function of immunosuppressive cytokines were suppressed and the proinflammatory cytokine’s secretion and function were enhanced. Therefore the immune response was activated and resulted in suppressing the recurrence and growth of GBM. We hypothesize that post-operative meningitis might improve the survival of patients with GBM. The reason maybe exists in that infection activate immune responses in the CNS and enhance the power to kill the cancer cells. Our hypothesis might provide a novel therapeutic strategy for patients with GBM. And we believe the relationship between immune and cancer cells deserve further study.

Design, synthesis and evaluation of novel diphenyl ether derivatives against drug susceptible and resistant strains of Mycobacterium tuberculosis

In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a–f, 6a–f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug‐susceptible, isoniazid‐resistant, and multidrug‐resistant strains of Mycobacterium tuberculosis with MIC values of 1.56 μg/ml (6b), 6.25 μg/ml (6a–d), and 3.125 μg/ml (6b–c), respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50 > 300 μg/ml) against Vero and HepG2 cells. Reverse phase HPLC method was used to probe the physicochemical properties of the synthesized compounds. This series of compounds demonstrated comparatively low logP values. pKa values of representative compounds indicated that they were weak acids. Additionally, in vitro human liver microsomal stability assay confirmed that the synthesized compounds possessed acceptable stability under study conditions. The present study thus establishes compound 6b as the most promising antitubercular agent with acceptable drug‐likeness.