BITS Faculty Publications
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Item Evaluation of Antioxidant Potential of Barleria prionitis Leaf and Stem(iMedPub, 2014) Mahesh, R.The aim of the present work was to investigate the antioxidant potential of different extracts of Barleria prionitis leaf and stem. The successive extraction of individual plant part was carried out using solvents of different polarity viz. n-hexane, ethyl acetate, methanol and water. The preliminary Phytochemical screening of all the extracts was done. The present total phenolic contents were estimated by Folin- Ciocalteu reagent method and expressed as μg/mg of gallic acid equivalent. The antioxidant potential and reducing power of all the prepared extracts were measured against DPPH as compared to standard ascorbic acid, and BHA respectively. The result data indicated that the phenolic contents were higher in methanolic extracts of leaf (103.51±0.38 mg/g) followed by ethyl acetate (52.91±0.28 mg/g), aqueous extract (42.02±0.36 mg/g) and n-Hexane (12.48±0.27 mg/g). The similar pattern in stem part was also observed, i.e. methanolic extracts (94.37±0.18 mg/g), ethyl acetate (44.31±0.45 mg/g), water (32.82±0.31 mg/g) and n-Hexane (8.33±0.21 mg/g). The antioxidant capacity of methanolic extract of both the part, i.e. leaf and stem were founded highest as IC50 values were 63.41±0.32, 81.69±0.40 respectively. The reducing power was also highest in the methanol extract of both parts. The result data conclude that the higher antioxidant as well as reducing power may be due to present phenolic contents.Item Rational design, synthesis and in vitro evaluation of allylidene hydrazinecarboximidamide derivatives as BACE-1 inhibitors(Elsevier, 2016-01) Mahesh, R.BACE-1 (β-secretase) is considered to be one of the promising targets for treatment of Alzheimer’s disease as it catalyzes the rate limiting step of Aβ-42 production. Herein, we report a novel class of allylidene hydrazinecarboximidamide derivatives as moderately potent BACE-1 inhibitors, having aminoguanidine substitution on allyl linker with two aromatic groups on either side. A library of derivatives was designed based on the docking studies, synthesized and evaluated for BACE-1 inhibition in vitro. The designed ligands displayed interactions with the catalytic aspartate dyad through guanidinium functionality. Further, the aromatic rings placed on either side of the linker occupied S1 and S3 active site regions contributing to the activity. These ligands were also predicted to follow Lipinski rule and cross blood brain barrier. Compound 2.21, having high docking score, was found to be most active with IC50 of 6.423 μM indicating good correlation with docking prediction.Item Dynamin Functions and Ligands: Classical Mechanisms Behind(American Society for Pharmacology and Experimental Therapeutics, 2017-02) Mahesh, R.Dynamin is a GTPase that plays a vital role in clathrin-dependent endocytosis and other vesicular trafficking processes by acting as a pair of molecular scissors for newly formed vesicles originating from the plasma membrane. Dynamins and related proteins are important components for the cleavage of clathrin-coated vesicles, phagosomes, and mitochondria. These proteins help in organelle division, viral resistance, and mitochondrial fusion/fission. Dysfunction and mutations in dynamin have been implicated in the pathophysiology of various disorders, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Charcot-Marie-Tooth disease, heart failure, schizophrenia, epilepsy, cancer, dominant optic atrophy, osteoporosis, and Down’s syndrome. This review is an attempt to illustrate the dynamin-related mechanisms involved in the above-mentioned disorders and to help medicinal chemists to design novel dynamin ligands, which could be useful in the treatment of dynamin-related disorders.Item Traumatic brain injury: severity, pathophysiology and neurobehavioural outcome(Pharmacologyonline, 2010) Mahesh, R.At least 1.4 million people die, or receive hospital or emergency care every year in the United States as a result of traumatic brain injury (TBI). Many more are treated in other settings or receive no treatment at all. Thus TBI is often unidentified, with subsequent cognitive, behavioral, emotional and physical sequelae that are not linked to the injury. Yet, over 5.3 million Americans live with TBI-related disabilities that interfere with their overall performance and social roles within the community. Traumatic brain injury is a leading cause of death and disability in developed countries. Damage caused by focal and diffuse lesions produces symptoms involving most major medical systems as well as symptoms of neuro-logical and psychological origin. Recent published articles on emotional and behavioural consequences of traumatic brain injury (TBI) are reviewed. The ranges of clinical problems reviewed include depression and anxiety, post-traumatic stress symptoms, as well as the TBI animal model.Item Newer targets for cancer: a review(Pharmacologyonline, 2011) Mahesh, R.Cancer is the leading cause of death worldwide. Over 2 million people in the UK alone are currently living with the consequences of cancer and its treatment and this figure is projected to grow at more than 3% in a year. However, despite major improvements in diagnostic tools, patient management and cytotoxic therapies during the past quarter century, the impact on longterm survival has been modest. As our knowledge of the molecular biology of cancers in general has increased exponentially during the last 2 decades, multiple new targets have been identified and they provide a host of new approaches. This review addressed some of the recent approaches and idea for the treatment of cancer.Item Depression: Current Therapy and ovel Anti-depressant Drug Targets(Pharmacologyonline, 2009) Mahesh, R.Affective disorders such as depression and anxiety are a major cause of disability and place a burden on society from both economic and social perspectives. In spite of over 50 years of effort in drug discovery and development, a substantial increase in the efficacy of antidepressant therapies has not been achieved, although improvements in safety and tolerability have been observed in newer drug therapies. Despite the advances in the anti-depressant therapy with various serotonergic and noradrenergic agents, a substantial unmet medical need in the treatment of depressive illness remains. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. At one end of the spectrum is combination therapies that maintain the benefits associated with standard anti-depressant drugs and at the other end more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis could fit to the need of antidepressant therapy. This review summarizes the pathological detail of depression, current anti-depressant therapy and development of non-monoamine-based antidepressants, and provides a progress report on some of the most promising current strategiesItem Depression Associated Disorders: Comorbidity, eurobiological and eurobehavioural Link(Pharmacologyonline, 2010) Mahesh, R.Comorbidity commonly refers to the co-occurrence (or dual diagnosis) of two disorders or syndromes in the same patient, regardless of whether the disorders are coincidentally or causally linked. Indeed, illnesses have been classified in discrete diagnostic categories although no sharp discontinuities in symptom distributions are observed across most mental disorders. Depression is a relatively common psychiatric comorbididy of most neurological disorders, with prevalence rates ranging between 20 and 50% among patients with stroke, multiple sclerosis, epilepsy, Parkinson’s disease and dementia. Furthermore, depression is an independent predictor of poor quality of life in these patients and has a negative impact on the response to treatment, course and recovery of neurological deficits. Comorbid depressive disorders in neurologic patients can be indistinguishable to the primary mood disorders and may mimic major depression, dysthymic, minor depressive, and bipolar disorders described in the DSM-IV classification of mood disorders. In addition, the great overlap of medical and psychiatric symptoms in depression and neurologic disorders may lead to both false-positive and false-negative diagnoses of depression. Patient with comorbid condition have lower response rate and /or a longer time to response, greater reports of side effect early in treatment and greater likely hood of dropping out. In this review, we focus on comorbid disorder associated with depression.Item TAFI: A Potential Target for Fibrinolytic Drugs(Pharmacologyonline, 2009) Mahesh, R.Thrombosis is one the major cause of death worldwide. Clinicians and haematologists are confronted more and more with diagnosis and management of patients with venous and arterial thrombo-embolic phenomenon. In the recent past there have been major advancements in the field of the aetio-pathogenisis of haemostasis. Thrombosis occurs when there is an imbalance between pro-thrombotic and anti-thrombotic mechanisms. Thrombin activatable fibrinolysis inhibitor (TAFI) is a potential target to treat various thrombotic as well as metabolic disorders. TAFI is a Carboxypeptidase B like enzyme with a mol. wt. 60 kDa and it is activated by thrombin-thrombomodulin complex to activated form TAFIa which cleaves carboxyl-terminal lysine residues from partially degraded fibrin, rendering it resistant to fibrinolysis by endogenous tissue plasminogen activator (tPA). Thus inhibition of TAFI with an appropriate TAFI inhibitor will be an attractive strategy for various thrombotic as well as metabolic disorders in which levels of TAFI is highly elevated like deep vein thrombosis, angina pectoris, obesity and non insulin dependent diabetes mellitus.Item Review: The auspicious role of the 5-HT3 receptor in depression: a probable neuronal target?(Sage, 2010-02) Mahesh, R.The serotonergic mechanisms have been successfully utilized by the majority of antidepressant drug discovery programmes, while the search for newer targets remains persistent. The present review focused on the serotonin type-3 receptor, the only ion channel subtype in the serotonin family. Behavioural, neurochemical, electrophysiological and molecular analyses, including the results from our laboratory, provided substantial evidence that rationalizes the correlation between serotonin type-3 receptor modulation and rodent depressive-like behaviour. Nevertheless, the reports on polymorphism of serotonin type-3 receptor genes and data from clinical studies (on serotonin type-3 receptor antagonists) were insufficient to corroborate the involvement of this receptor in the neurobiology of depression. The preclinical and clinical studies that have contradicted the antidepressant-like effects of serotonin type-3 receptor antagonists and the reasons underlying such disagreement were discussed. Finally, this critical review commended the serotonin type-3 receptor as a candidate neuronal antidepressant drug target.Item An unusual case of xylophagia (paper-eating)(Mednow Pubications, 2013) Mahesh, R.Xylophagia is a condition involving the consumption of paper and form of eating disorder known as pica. Pica is an unusual craving for ingestion of either edible or inedible substances. Inhalants are volatile substances, which produce chemical vapors that can be inhaled to induce a psycho-active or mind altering effect. Although, pica is not linked to solvent abuse, here we report an adolescent case of paper-eating with solvent dependence.