Pharmacokinetics-Pharmacodynamics Driven Approach for Lead Optimization in Anti-Mycobacterial and Anti-Malarial Drug Discovery

Ph.DDOCTOR OF PHILOSOPH

A study of anti-inflammatory activity of the benzofuran compound (3,4-dihydro 4-oxo-benzofuro [3,2-d] pyrimidine-2-propionic acid) in chronic model of inflammation

Background: Benzofuran compounds are shown to have pharmacological properties such as antiarrhythmic, antidepressant, antifungal, and antibacterial activity. Some studies conducted on them have revealed that they are having anti-inflammatory property also. Hence, we carried out this study to know whether the benzofuran compound 3, 4-dihydro 4-oxo-benzofuro (3, 2-d) pyrimidine-2-propionic acid has got anti-inflammatory activity against chronic inflammation.Methods: Wistar albino rats were treated with benzofuran compound under study and phenylbutazone in the dose of 100 mg\kg, orally with 2% gum acacia as suspending agent and the effects were observed in chronic experimental model of inflammation namely, cotton pellet induced granuloma model.Results: In the present study, it was shown that the benzofuran compound under study has got significant anti-inflammatory activity against the chronic model of inflammation.Conclusion: Our experiment shows that the benzofuran compound under study has got significant anti-inflammatory activity and may, as well become an additional anti-inflammatory drug if further studies are conducted in this direction involving human beings

Screening of benzofuran compound 3-acetamido-2-p-anisoyl benzofuran for anti-inflammatory activity in acute models of inflammation

Background: Benzofurans are colourless solid compounds which are derived from coal tar. They have been shown to have many properties which are relevant to the field of pharmacology. For example they have significant antibacterial, antifungal, antidepressant and anti-arrhythmic properties. In some of the studies carried out on them they have shown to have anti-inflammatory activity also. So this study was conducted to know if the compound 3-acetamido-2-p-anisoyl benzofuran has anti-inflammatory activity in acute inflammation.Methods: The benzofuran compound understudy and phenylbutazone were administered orally to wistar albino rats in the dose of 100 mg/kg body weight, with 2% gum acacia as suspending agent and the effects were observed in acute models of inflammation viz, carrageenin induced rat paw edema, and turpentine induced peritonitis.Results: The results of our study showed that the benzofuran compound under study has significant anti-inflammatory activity in both the experimental models of acute inflammation.Conclusions: Results from our study show that the compound under study has significant anti-inflammatory activity and further detailed works with this compound in different doses are needed

TO FUNCTIONING OF ECG OBSERVING DEVICE BY USING IOT TECHNOLOGY

This paper pro poses the layout of a wi-fi, locket sized Electrocardiogram (ECG) tracking tool, which is supposed to be utilized by coronary heart sufferers. The tool is capable of  obtaining affected individual’s ECG constantly and dynamically transmitting it to the affected individual’s cellular palms et, it is  interfaced to the tool thru a wi-fi channel like a  WIFI. The tool is capable of obtaining affected man or woman’s ECG continuously and dynamically transmitting it to the affected person’s cellular handset, which is interfaced to the tool through a wireless channel like an IOT. ECG obtained at the patient’s cell telephone is processed and in comparison with present ECG plots and abnormality if detected, a notification message is dispatched from an affected person’s cellular telephone to the cell Smartphone at the clinical-center and therefore essential treatment may be prescribed for the affected person. An Android application is present in the mobile telephone which plays this assignment

Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis

Current anti-trypanosomal therapies suffer from problems of longer treatment duration, toxicity and inadequate efficacy, hence there is a need for safer, more efficacious and 'easy to use' oral drugs. Previously, we reported the discovery of the triazolopyrimidine (TP) class as selective kinetoplastid proteasome inhibitors with in vivo efficacy in mouse models of leishmaniasis, Chagas Disease and African trypanosomiasis (HAT). For the treatment of HAT, development compounds need to have excellent penetration to the brain to cure the meningoencephalic stage of the disease. Here we describe detailed biological and pharmacological characterization of triazolopyrimidine compounds in HAT specific assays. The TP class of compounds showed single digit nanomolar potency against Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense strains. These compounds are trypanocidal with concentration-time dependent kill and achieved relapse-free cure in vitro. Two compounds, GNF6702 and a new analog NITD689, showed favorable in vivo pharmacokinetics and significant brain penetration, which enabled oral dosing. They also achieved complete cure in both hemolymphatic (blood) and meningoencephalic (brain) infection of human African trypanosomiasis mouse models. Mode of action studies on this series confirmed the 20S proteasome as the target in T. brucei. These proteasome inhibitors have the potential for further development into promising new treatment for human African trypanosomiasis

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria.

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves artemisinin-like kill kinetics in vitro with a parasite clearance time of \u3c24 h. A single dose of 30 mg/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance in drug selection studies and a long half-life (T1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials

48th Annual Convention of Computer Society of India

  This volume contains 85 papers presented at CSI 2013: 48th Annual Convention of Computer Society of India with the theme “ICT and Critical Infrastructure”. The convention was held during 13th –15th December 2013 at Hotel Novotel Varun Beach, Visakhapatnam and hosted by Computer Society of India, Vishakhapatnam Chapter in association with Vishakhapatnam Steel Plant, the flagship company of RINL, India. This volume contains papers mainly focused on Data Mining, Data Engineering and Image Processing, Software Engineering and Bio-Informatics, Network Security, Digital Forensics and Cyber Crime, Internet and Multimedia Applications and E-Governance Applications.This volume contains 88 papers presented at CSI 2013: 48th Annual Convention of Computer Society of India with the theme “ICT and Critical Infrastructure”. The convention was held during 13th –15th December 2013 at Hotel Novotel Varun Beach, Visakhapatnam and hosted by Computer Society of India, Vishakhapatnam Chapter in association with Vishakhapatnam Steel Plant, the flagship company of RINL, India. This volume contains papers mainly focused on Computational Intelligence and its applications, Mobile Communications and social Networking, Grid Computing, Cloud Computing, Virtual and Scalable Applications, Project Management and Quality Systems and Emerging Technologies in hardware and Software.

A study of anti-inflammatory activity of the benzofuran compound (3,4-dihydro 4-oxo-benzofuro [3,2-d] pyrimidine-2-propionic acid) in chronic model of inflammation

Background: Benzofuran compounds are shown to have pharmacological properties such as antiarrhythmic, antidepressant, antifungal, and antibacterial activity. Some studies conducted on them have revealed that they are having anti-inflammatory property also. Hence, we carried out this study to know whether the benzofuran compound 3, 4-dihydro 4-oxo-benzofuro (3, 2-d) pyrimidine-2-propionic acid has got anti-inflammatory activity against chronic inflammation.Methods: Wistar albino rats were treated with benzofuran compound under study and phenylbutazone in the dose of 100 mg\kg, orally with 2% gum acacia as suspending agent and the effects were observed in chronic experimental model of inflammation namely, cotton pellet induced granuloma model.Results: In the present study, it was shown that the benzofuran compound under study has got significant anti-inflammatory activity against the chronic model of inflammation.Conclusion: Our experiment shows that the benzofuran compound under study has got significant anti-inflammatory activity and may, as well become an additional anti-inflammatory drug if further studies are conducted in this direction involving human beings

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