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Kasa Shiva Raju Sandeep AnkiReddy Gowravaram Sabitha Vagolu Siva Krishna Dharmarajan Sriram Kunduru Bharathi Reddy Someswar Rao Sagurthi 《Bioorganic & medicinal chemistry letters》2019,29(2):284-290
A series of novel 1H-pyrrolo[2,3-d]pyrimidine-1,2,3-triazole derivatives have been synthesized in good to excellent yields. Through the copper-catalyzed azide-alkyne cycloaddition via reaction of 7-(prop-2-ynyl)-7H-pyrrolo[2,3-d]pyrimidine and aryl, heteroaryl and alkyl azides in the presence of CuSO4·5H2O and sodium ascorbate. These compounds were evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain. Most of these pyrrolopyrimidine-triazole hybrids exhibited good anti tubercular activity. The antimycobacterial assay results showed that the minimum inhibitory concentration of compounds 4q and 4r were 0.78?µg/mL. The molecular docking results also had shown highest Moldock score for same compounds. These novel compounds exhibited good inhibition activities and further structure-activity studies of the derivatives had shown promising features to use in antitubercular therapy. 相似文献
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Arash Boroumand Nasr Deepika Ponnala Someshwar Rao Sagurthi Ramesh Kumar Kattamuri Vijaya Kumar Marri Suresh Gudala Chandana Lakkaraju Srinivas Bandaru Anuraj Nayarisseri 《Bioinformation》2015,11(6):307-315
Mammalian target of rapamycin (mTOR) is a key regulator of cell growth, proliferation and angiogenesis. mTOR signaling is
frequently hyper activated in a broad spectrum of human cancers thereby making it a potential drug target. The current drugs
available have been successful in inhibiting the mTOR signaling, nevertheless, show low oral bioavailability and suboptimal
solubility. Considering the narrow therapeutic window of the available inhibitors, through computational approaches, the present
study pursues to identify a compound with optimal oral bioavailability and better solubility properties in addition ensuing high
affinity between FKBP12 and FRB domain of mTOR. Current mTOR inhibitors; Everolimus, Temsirolimus Deforolimus and
Echinomycin served as parent molecules for similarity search with a threshold of 95%. The query molecules and respective similar
molecules were docked at the binding cleft of FKBP12 protein. Aided by MolDock algorithm, high affinity compounds against
FKBP12 were retrieved. Patch Dock supervised protein-protein interactions were established between FRB domain of mTOR and
ligand (query and similar) bound and free states of FKBP12. All the similar compounds thus retrieved showed better solubility
properties and enabled better complex formation of mTOR and FKBP12. In particular Everolimus similar compound PubChem ID:
57284959 showed appreciable drugs like properties bestowed with better solubility higher oral bioavailability. In addition this
compound brought about enhanced interaction between FKBP12 and FRB domain of mTOR. In the study, we report Everolimus
similar compound PubChem ID: 57284959 to be potential inhibitor for mTOR pathway which can overcome the affinity and
solubility concerns of current mTOR drugs.
Abbreviations
mTOR - Mammalian Target of Rapamycin, FRB domain - FKBP12-rapamycin associated protein, FKBP12 - FK506-binding protein 12, OPLS - Optimized Potentials for Liquid Simulations, Akt - RAC-alpha serine/threonine-protein kinase, PI3K - phosphatidylinositide 3-kinases. 相似文献3.
Lova Satyanarayna Matsa Someswar Rao Sagurthi Venkateshwari Ananthapur Swapna Nalla Pratibha Nallari 《Gene》2014
Dilated cardiomyopathy (DCM) is a myocardial disease of unknown etiology with left ventricular dilatation and impaired myocardial contractility leading to heart failure. It is considered to be a multifactorial disorder with the interplay of both genetic and environmental factors. One of the possible genes implicated in DCM is endothelin 1 (EDN1). The genetic variants of EDN1 may be involved in the pathophysiology of DCM hence the entire EDN1 gene was screened to examine for the possible genotypic associations with DCM. A total of 115 DCM patients and 250 control subjects were included in the present study. PCR based SSCP analysis was carried out followed by commercial sequencing. Screening of EDN1 revealed two common and two rare polymorphisms. Allelic and genotypic frequencies were estimated in patient and control groups by appropriate statistical tests. The heterozygotes of insertion variation (+ 138A) were found to exhibit four-fold increase risk to DCM (OR = 4.12, 95% CI 2.10–8.08; p = 0.0001). The two rare variants (G>A transition (rs150035515) at c.90 and C>T transition (rs149399492) at c.119) observed in the present study were found to be unique in DCM. The secondary mRNA structures of these variations were found to have less free energy than wild type. The haplotype analysis revealed 4A–T to be risk haplotype for DCM (OR 5.90, 95% CI 2.29–15.25, p = 0.0001). In conclusion, EDN1 polymorphisms (+ 138A, A30A, T40I) appear to play a significant role in the pathogenesis of DCM, as they influence the stability of protein. The increased EDN1 production may lead to constriction of coronary arteries, reducing coronary blood flow which may in turn increase the load on left ventricle, impairing contractility of the heart resulting in a DCM phenotype, an end stage of heart failure. 相似文献
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Kumar Janish Qureshi Rahila Sagurthi Someswar R. Qureshi Insaf Ahmed 《International journal of peptide research and therapeutics》2021,27(2):941-956
International Journal of Peptide Research and Therapeutics - The COVID-19 disease is caused by SARS-CoV-2 and spreading rapidly worldwide with extremely high infection rate. Since effective and... 相似文献
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Sudhakar Mokenapelli Gutam Madhu Yerrabelli Jayaprakash Rao Irlapati Vamshi Krishna Gorityala Neelima Sagurthi Someswar Rao Chitneni Prasad Rao 《Russian Journal of Bioorganic Chemistry》2020,46(5):845-855
Russian Journal of Bioorganic Chemistry - A new series of 2,5-regioselective benzofuran-tetrazole hybrids (XIIIa–XIIIp) were synthesised from 2H-chromene-3-carbonitriles (IXa), (IXb) in multi... 相似文献
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Rahila Qureshi Malini Devi Alaparthi Prathyusha Sai Eligati Syed Rizwan Hasan Razvi Komal Paresh Walvekar Mohammad Afraa Someswar Rao Sagurthi 《Bioinformation》2020,16(11):942
Leishmaniasis is one of the most neglected diseases with high morbidity and mortality rate. Severe side effects with existing drug and lack of proper vaccine encouraged us to design alternative models to combat the disease. We showed that PP1 of Leishmania donovani mediates immunomodulation in host macrophages needed for parasite survival. Therefore, it is of interest to report the molecular docking analysis of 512 isoflavone derivatives with the phosphatase 1 protein from Leishmania donovani to highlight compound 362 (5-hydroxy-5-{9-[2-methoxy-2-(2-methylfuran-3-yl) ethyl]-1H, 3H, 4H, 10bH-pyrano[4,3-c]chromen-3-yl}pentanoic acid) having good binding features and acceptable ADMET properties for further consideration. 相似文献
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