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A facile one-pot synthesis of 3,5-diarylisoxazoles from α,β-unsaturated ketones and hydroxylamine hydrochloride is reported. The reaction is efficiently promoted by catalytic CuBr2 and Oxone to afford the desired products mostly in high yields and in relatively short time. The mild nature of the synthesis and short reaction time are notable advantages of the developed protocol. This protocol is effective toward various substrates having different functionalities.

To measure the impact of 12 weeks of physical exercise as complementary management strategy on quality of life (QOL) in people with epilepsy (PWE).In a parallel-group, randomized controlled study with blinded outcome assessment, PWE of 18-65 years old, smartphone users were randomized into two groups. The exercise group was advised minimum 150 min per week of moderate-intense aerobic activity, as per current WHO recommendation [1], in addition to standard medical care; the control group received only standard medical care. QOL was assessed using Quality of Life in Epilepsy (QOLIE-31) inventory [2,3]; physical activity, with Global Physical Activity Questionnaire version 2 (GPAQ), and Pedometer Step Counter (a smartphone-based activity tracker application), at baseline and after 12 weeks. Body weight, body mass index, seizure frequency, and stigma scores (Epilepsy Stigma Scale Austin and colleagues) [4] were also noted.One hundred and seventeen PWE were recruited (58 exercise, 59 control). Although there was an improvement in the physical activity correlates after 12 weeks compared to mean values at baseline, the differences were not significant between the groups. The total QOL mean scores at baseline in the exercise and control groups were 64.9 and 63.7 (p = 0.597) and after 12 weeks, 68.4 and 66.9 (p = 0.660), respectively. However, intragroup comparison of energy/fatigue score in the exercise group showed significant change with a p value of 0.009 and intragroup comparison of Overall QOL score in the control group showed a significant change with a p value of 0.003. Similar improvement was seen in stigma scores (p = 0.500) and seizure frequency (p = 0.388) at 12 weeks in exercise and control groups. After 12 weeks, mean values of METS ((metabolic equivalents) were 794.81 and 714.27 (p = 0.159), steps per day were 4018.32 and 3730.0 (p = 0.314), calories spent per day were 173.85 and 159.68 (p = 0.320 and distance walked per day in meters were 2576.52 and 2198.42 (p = 0.072), in the exercise and control groups, respectively.Regular physical activity for at least 150 min per week, in the form of moderate-intense aerobic exercises resulted in positive yet non-significant improvement of QOL, seizure frequency, and stigma in PWE.

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria.

NO has many physiological roles; in inflammation, pain, rheumatoid arthritis, immune system, gastroprotection, as antioxidant and reported to be a free radical scavenger.Intensive research on the biological functions of NO and other reactive nitrogen oxide species demands exogenous sources of NO donors as research tools and pharmaceuticals. Since the mid-1980s, the development of new NO donors has offered several advantages over theprevious NO donors, such as spontaneous release of NO, donation of NO under controlled rates, and even the targeting of NO to certain tissues. Nitric oxide releasing derivatives of conventional NSAIDs have been synthesized not only to avoid gastrotoxicity, but also for making them fit for topical delivery, targeting them to brain and increase their analgesic and anti-inflammatory activity. "Hybrid nitrates" have vital role in different like NSAIDs, Anti-platelet, Antileukemic, Glaucoma, Antihypertensive, Antimalarial etc.

In view of paucity of studies on predictors of hyponatremia in tuberculous meningitis (TBM) and its influence on outcome, this study was undertaken.To study the frequency, predictors and prognosis of hyponatremia in TBM.In this prospective hospital based study, 76 patients with TBM (definite 18 and probable 58) were enrolled. The severity of meningitis was graded as I-III and hyponatremia as severe (120mEq/L), moderate (120-129mEq/L) or mild (130-134mEq/L). Hospital death was noted and functional outcome was assessed by modified Rankin Scale (mRS) on discharge.34 (44.7%) TBM patients had hyponatremia (mild 3, moderate 23 and severe 8). Hyponatremia was due to cerebral salt wasting in 17, syndrome of inappropriate secretion of antidiuretic hormone in 3 and miscellaneous causes in 14 patients. Hyponatremia was related to GCS score and basal exudates. Outcome of TBM was related to duration of hospitalization, GCS score, focal deficit, mechanical ventilation, severity of TBM, age and comorbidities. Cerebral salt wasting was related to severity of TBM.Hyponatremia occurred in 44.7% of TBM patients. Cerebral salt wasting was the commonest cause of hyponatremia and was related to the severity of TBM.

Morpholine is a versatile moiety, a privileged pharmacophore and an outstanding heterocyclic motif with wide ranges of pharmacological activities due to different mechanisms of action. The ability of morpholine to enhance the potency of the molecule through molecular interactions with the target protein (kinases) or to modulate the pharmacokinetic properties propelled medicinal chemists and researchers to synthesize morpholine ring by the efficient ways and to incorporate this moiety to develop various lead compounds with diverse therapeutic activities. The present review primarily focused on discussing the most promising synthetic leads containing morpholine ring along with structure-activity relationship (SAR) to reveal the active pharmacophores accountable for anticancer, anti-inflammatory, antiviral, anticonvulsant, antihyperlipidemic, antioxidant, antimicrobial and antileishmanial activity. This review outlines some of the recent effective chemical synthesis for morpholine ring. The review also highlighted the metabolic liability of some clinical drugs containing this nucleus and various researches on modified morpholine to enhance the metabolic stability of drugs as well. Drugs bearing morpholine ring and those under clinical trials are also mentioned with the role of morpholine and their mechanism of action. This review will provide the necessary knowledge base to the medicinal chemists in making strategic structural changes in designing morpholine derivatives.

Objective Aerva lanata (Linn) Juss ex Schult, family Amaranthaceae, is a common wayside weed. The herb is accepted by the Ayurvedic Formulary of India. This study was undertaken to establish morphoanatomic and physiochemical standards of A. lanata . Methods Leaf constants and high-performance thin layer chromatography fingerprint profiles of A. lanata were performed. Results and conclusion The physico–chemical, morphologic, and histologic parameters presented in this paper may be proposed as standards to establish the authenticity of A. lanata and help differentiate it from other species such as Aerva tomentosa .

A convenient synthesis of 1,5-fused 1,2,4-triazoles from readily available N-heteroaryl benzamidines is reported. The reaction is efficiently promoted by trichloroisocyanuric acid to afford the desired products, mostly in high yields and in relatively short time, through direct metal-free oxidative N–N bond formation. The mild nature of the synthesis and short reaction time are notable advantages of the developed protocol. This protocol is effective toward various substrates having different functionalities.

Indole is a versatile pharmacophore, a privileged scaffold and an outstanding heterocyclic compound with wide ranges of pharmacological activities due to different mechanisms of action. It is an superlative moiety in drug discovery with the sole property of resembling different structures of the protein. Plenty of research has been taking place in recent years to synthesize and explore the various therapeutic prospectives of this moiety. This review summarizes some of the recent effective chemical synthesis (2014-2018) for indole ring. This review also emphasized on the structure-activity relationship (SAR) to reveal the active pharmacophores of various indole analogues accountable for anticancer, anticonvulsant, antimicrobial, antitubercular, antimalarial, antiviral, antidiabetic and other miscellaneous activities which have been investigated in the last five years. The precise features with motives and framework of each research topic is introduced for helping the medicinal chemists to understand the perspective of the context in a better way. This review will definitely offer the platform for researchers to strategically design diverse novel indole derivatives having different promising pharmacological activities with reduced toxicity and side effects.

The temperature-dependent formation of a remarkably stable enol from the reaction of EtMgBr with a 1,2-diester was accidentally discovered. This compound was spectroscopically characterized (1H and 13C NMR, IR), and both methyl carbonate and trimethylsilyl ether derivatives were prepared. A mechanism for the selective formation of the stable enol ester and its corresponding keto form was suggested, and the kinetic stability of the enol was also documented. The generality of the observation of such a stable enol ester was demonstrated with the use of other Grignard reagents, and also other 1,2-diesters. The reaction of EtMgBr with a series of 1,2-amide esters also produced stable enol amides. The remarkable stability of the enol esters was attributed to the steric hindrance present in the aryl ester moiety of these compounds, and further studies will address the origin of this effect.

The aim of the present work is to investigate the utility of redox chemical delivery prodrug approach for the targeted and sustained release of an alkylating anticancer agent in the brain. The N-methyl-1,4-dihydronicotinate ester of an alkylating nitrogen mustard NM-CDS (4) was synthesized in three step reactions. Structures of all the synthesized compounds were confirmed by UV, IR, (1H&13C) NMR and CHN elemental studies. In vitro chemical oxidation studies with silver nitrate of NM-CDS (4) indicated that it can be readily converted into its corresponding quaternary salt (3) with half life of 8 min. In vitro biological oxidation studies showed facile oxidation in biological media and rate of oxidation followed pseudo first-order kinetics with reasonable half-lives of 32.5 min in rat blood, 24.2 min in human blood and 19.4 min in brain homogenate. The in vivo studies on Sprague–Dawley rats were performed. The NM-CDS (4) at a dose of 40 mg/kg, was injected into rats. At selected time intervals, blood samples and the brains were collected and analyzed by UV spectrophotometer. The results demonstrated that NM-CDS (4) was able to cross the blood–brain barrier (BBB) at detectable concentration, oxidized to its active quaternary salt (Q-salt) (3) and sustained there for some period of time. The in silico ADME descriptors required for CNS activity were determined by computational, online (Molinspiration) and QikProp 3.2 software (Schrodinger, USA) that further indicated that NM-CDS (4) has a good potential to cross the BBB and show CNS antitumor activity.