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Patil V.M.,Bharat Institute of Technology
EXS | Year: 2012

Matrix metalloproteinases (MMPs) regulate a wide range of biological functions, but their overactivation leads to a wide array of disease processes such as rheumatoid arthritis, ostereoarthritis, tumor metastatis, multiple sclerosis, congestive heart failure, and a host of others. Therefore, the study of MMP inhibitors has evoked a great interest among scientists. As a result, different groups of compounds have been synthesized and studied for MMP inhibitions. Among them, a large number of structurally novel sulfonamide derivatives have been reported to be potential MMP inhibitors, but only a few have reached to the final stage of clinical trial. Many authors have made quantitative structure-activity relationship (QSAR) studies on them to provide the guidelines to design more potent MMP inhibitors. This article presents a comprehensive review on all such QSARs reported with critical assessment in order to provide a deeper insight into the structure-activity relationship of sulfonamides which can be used to synthesize highly potential drugs of pharmaceutical importance. Source


Gupta S.,Neuropharmacology Laboratory | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
European Journal of Pharmacology | Year: 2014

Huntingtons disease (HD), a devastating neurodegenerative disorder, is characterized by weight loss, impairment of motor function, cognitive dysfunction, neuropsychiatric disturbances and striatal damage. Phosphodiesterase-1 (PDE1) has been implicated in various neurological diseases. Mitochondrial potassium channels in the brain take part in neuroprotection. This study has been structured to investigate the role of vinpocetine, a selective PDE1 inhibitor as well as nicorandil, selective ATP sensitive potassium (KATP) channel opener in 3-nitropropionic acid (3-NP) induced HD symptoms in rats. Systemic administration of 3-NP significantly, reduced body weight, impaired locomotion, grip strength and impaired cognition. 3-NP elicited marked oxidative stress in the brain (enhanced malondialdehyde-MDA, reduced glutathione-GSH content, superoxide dismutase-SOD and catalase-CAT), elevated brain acetylcholinesterase activity and inflammation (myeloperoxidase-MPO), with marked nitrosative stress (nitrite/nitrate) in the brain. 3-NP has also induced mitochondrial dysfunction (impaired mitochondrial NADH dehydrogenase-complex I, succinate dehydrogenase-complex II and cytochrome oxidase-complex IV) activities in the striatum of the rat. Tetrabenazine was used as a positive control. Treatment with vinpocetine, nicorandil and tetrabenazine ameliorated 3-NP induced reduction in body weight, impaired locomotion, grip strength and impaired cognition. Treatment with these drugs reduced brain striatum oxidative (MDA, GSH, SOD and CAT) and nitrosative (nitrite/nitrate) stress, acetylcholinesterase activity, inflammation and mitochondrial dysfunctions. These results indicate that vinpocetine, a selective PDE1 inhibitor and nicorandil, a K ATP channel opener have attenuated 3-NP induced experimental HD. Hence, pharmacological modulation of PDE1 as well as KATP channels may be considered as potential research targets for mitigation of HD. © 2014 Elsevier B.V. Source


Sharma B.,Punjabi University | Sharma B.,Bharat Institute of Technology | Singh N.,Punjabi University
Pharmacology Biochemistry and Behavior | Year: 2013

Cognitive disorders are likely to increase over the coming years (5-10). Vascular dementia (VaD) has heterogeneous pathology and is a challenge for clinicians. Current Alzheimer's disease drugs have had limited clinical efficacy in treating VaD and none have been approved by major regulatory authorities specifically for this disease. Role of iNOS and NADPH-oxidase has been reported in various pathological conditions but there role in hypertension (Hypt) induced VaD is still unclear. This research work investigates the salutiferous effect of aminoguanidine (AG), an iNOS inhibitor and 4′-hydroxy-3′- methoxyacetophenone (HMAP), a NADPH oxidase inhibitor in Hypt induced VaD in rats. Deoxycorticosterone acetate-salt (DOCA-S) hypertension has been used for development of VaD in rats. Morris water-maze was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Mean arterial blood pressure (MABP), oxidative stress [aortic superoxide anion, serum and brain thiobarbituric acid reactive species (TBARS) and brain glutathione (GSH)], nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity-AChE) were also measured. DOCA-S treated rats have shown increased MABP with impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS, and brain AChE activity. AG as well as HMAP significantly convalesce Hypt induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that AG, an iNOS inhibitor and HMAP, a NADPH-oxidase inhibitor may be considered as potential agents for the management of Hypt induced VaD. © 2012 Elsevier Inc. Source


Tiwari B.K.,Translam Institute of Pharmaceutical Education and Research | Khosa R.L.,Bharat Institute of Technology
Internet Journal of Tropical Medicine | Year: 2010

The flower heads of Sphaeranthus indicus Linn (Asteraceae) a traditional Indian medicinal plant is commonly used to nourish and improve the liver conditions. This study was designed to evaluate the hepatoprotective and antioxidant effect of aqueous (AQS) and methanolic (MES) extract of flower heads of Sphaeranthus indicus on Paracetamol (APAP)-induced hepatotoxicity in rat's in-vivo. Activities of liver marker enzymes, glutamate-oxaloacetate transaminase (SGOT) glutamate pyruvate transaminase (SGPT), acid phosphatase (ACP) and alkaline phosphatase (ALP) bilirubin and total protein at an oral dose of MES (300mg/kg) showed a significant hepatoprotective effect in comparison with the same dose of aqueous extract. This fact was also confirmed by studying the liver histopathology of treated animals. As Regards the antioxidant activity, MES exhibited a significant effect (P < 0.05) showing increasing levels of superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxides (GPX) by reducing malondialdehyde (MDA) levels. © Internet Scientific Publications, LLC., 1996 to 2010. Source


Singh P.,Bharat Institute of Technology | Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Physiology and Behavior | Year: 2015

Cerebrovascular and cardiovascular diseases are stated as important risk factors of vascular dementia (VaD) and other cognitive disorders. In the central nervous system, melatonin (MT1/MT2) as well as serotonin subtype 2C (5-HT2C) receptors is pharmacologically associated with various neurological disorders. Brain mitochondrial potassium channels have been reported for their role in neuroprotection. This study has been structured to investigate the role of agomelatine, a melatonergic MT1/MT2 agonist and nicorandil, a selective ATP sensitive potassium (KATP) channel opener in renal artery ligation (two-kidney-one-clip: 2K1C) hypertension induced endothelial dysfunction, brain damage and VaD. 2K1C-renovascular hypertension has increased mean arterial blood pressure (MABP), impaired memory (elevated plus maze and Morris water maze), endothelial function, reduced serum nitrite/nitrate and increased brain damage (TTC staining of brain sections). Furthermore, 2K1C animals have shown high levels of oxidative stress in serum (increased thiobarbituric acid reactive species-TBARS with decreased levels of glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), in the aorta (increased aortic superoxide anion) and in the brain (increased TBARS with decreased GSH, SOD and CAT). 2K1C has also induced a significant increase in brain inflammation (myeloperoxidase-MPO levels), acetylcholinesterase activity (AChE) and calcium levels. Impairment in mitochondrial complexes like NADH dehydrogenase (complex-I), succinate dehydrogenase (complex-II) and cytochrome oxidase (complex-IV) was also noted in 2K1C animals. Administration of agomelatine, nicorandil and donepezil significantly attenuated 2K1C-hypertension induced impairments in memory, endothelial function, nitrosative stress, mitochondrial dysfunction, inflammation and brain damage. Therefore, modulators of MT1/MT2 receptors and KATP channels may be considered as potential agents for the management of renovascular hypertension induced VaD. © 2015 Elsevier Inc. Source

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