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Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.

A series of new imidazo[1,2-a]pyridine linked with thiazole/thiophene motif through a keto spacer were synthesized and tested for their cytotoxic potential against three human cancer cell lines including A549, HeLa and U87-MG using MTT assay. Compounds A2, A3, A4, C1 and C2 showed cytotoxicity against all the three cell lines. The selectivity index for compound A4 for A549 and HeLa cells was comparable to that of doxorubicin. Among the synthesized compounds, B5 showed the maximum inhibition of NF-κB activity as ascertained by NF-κB reporter assay (IC 50  = 6.5 ± 0.6 µM). Treatment of NCI-H23 cells (EGFR overexpressed, KRAS G12V mutant) with erlotinib and gefitinib along with compounds A4 and B5 indicated synergistic and additive potential of combination therapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats., (Copyright © 2015. Published by Elsevier Ltd.)

Here we report novel thiazole-thiophene conjugates as adenosine receptor antagonists. All the molecules were evaluated for their binding affinity for adenosine receptors. Most of the molecules were found to interact with the A1, A2A and A3 adenosine receptor subtypes with good affinity values. The most potent and selective compound 8n showed an A3Ki value of 0.33μM with selectivity ratios of >90 versus the A1 and >30 versus the A2 subtypes. For compound 8n docking studies into the binding site of the A3 adenosine receptor are provided to visualize its binding mode., (Copyright © 2015. Published by Elsevier Ltd.)

Introduction: Low back pain is one of the common conditions of loco motor system disorder, affects people during their productive life. About 40% cases of low back pain are of radicular in origin and considered under the umbrella of sciatic syndrome. It is a pain dominant disease and reduces human activity considerably in terms of personal as well as social and professional life. The condition resembles disease Gridhrasi mentioned in Ayurveda under the umbrella of Vatavyadhi, and here piercing type of pain which restricts the movement of the affected leg, make his walking pattern-like bird vulture and put him in disgraceful condition., Aim: To assess the effect of Vatari Guggulu on the management of Gridhrasi., Materials and Methods: A total of 40 patients of Gridhrasi were registered and Vatari Guggulu 3 tablet (500 mg each) twice a day was administered before meal with lukewarm water for 30 days., Results and Conclusions: About 32.35% of the patient improved moderately while mild improvement was observed in 47.09% of the patients. The drug has shown better effect on patients of Vata Kaphaja type of Gridhrasi in comparison of Vataja type of Gridhrasi.

The stability of the drug actarit was studied under different stress conditions like hydrolysis (acid, alkaline and neutral), oxidation, photolysis and thermal degradation as recommended by International Conference on Harmonization (ICH) guidelines. Drug was found to be unstable in acidic, basic and photolytic conditions and produced a common degradation product while oxidative stress condition produced three additional degradation products. Drug was impassive to neutral hydrolysis, dry thermal and accelerated stability conditions. Degradation products were identified, isolated and characterized by different spectroscopic analyses. Drug and the degradation products were synthesized by a new route using green chemistry. The chromatographic separation of the drug and its impurities was achieved in a phenomenex luna C18 column employing a step gradient elution by high performance liquid chromatography coupled to photodiode array and mass spectrometry detectors (HPLC-PDA-MS). A specific and sensitive stability-indicating assay method for the simultaneous determination of the drug actarit, its process related impurities and degradation products was developed and validated.

Irritable bowel syndrome (IBS) is one of the most common conditions encountered in clinical practice but one of the least well understood. Symptoms of this disorder are chronic, sometimes severe and often respond poorly to treatment, resulting in reduced quality of life. There is no specific test for IBS, although diagnostic tests may be performed to rule out other problems. In present clinical trial 51 patients of IBS were registered out of which 46 patients completed the treatment. Bilvadileha was administered for the duration of 12 weeks. The therapy showed statistically significant improvement in all the clinical features of IBS as well as in the IBS severity score.

Acne is a common skin problem that affects almost 85% of teenagers, mostly occurs on face and some time on chest and upper back too. This condition resembles with Yauvanapidika described in Ayurveda under the caption of Kshudraroga. In this study, 50 patients with symptoms of Yauvanapidika were treated in two groups. In Group A, patients were given local application of Shalmalyadilepa twice a day with milk, while in Group B patients were given 2 gm of Guduchyadivati thrice along with local application of Shalmalyadilepa. At the end of treatment, Group B showed better improvement in comparison to Group A.