School Of Basic And Applied Sciences

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Author: search.filters.author.Sharma S.Has files: No

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    E-pharmacophore guided discovery of pyrazolo[1,5-c]quinazolines as dual inhibitors of topoisomerase-I and histone deacetylase
    (Academic Press Inc., 2020) Joshi G.; Kalra S.; Yadav U.P.; Sharma P.; Singh P.K.; Amrutkar S.; Ansari A.J.; Kumar S.; Sharon A.; Sharma S.; Sawant D.M.; Banerjee U.C.; Singh S.; Kumar R.
    In the quest to ameliorate the camptothecin (CPT) downsides, we expedite to search for stable non-CPT analogues among 11 motifs of pyrazoloquinazolines reported. E-pharmacophore drug design approach helped filtering out pyrazolo[1,5-c]quinazolines as Topoisomerase I (TopoI) 'interfacial' inhibitors. Three compounds, 3c, 3e, and 3l were shown to be potent non-intercalating inhibitors of TopoI specifically and showed cancer cell-specific cytotoxicity in lung, breast and colon cancer cell lines. The compounds induced cell cycle arrest at S-phase, mitochondrial cell death pathway and modulated oxidative stress in cancer cells. Furthermore, a preliminary study was conducted to explore the feasibility of these compounds to be developed as dual TopoI-HDAC1 (histone deacetylase 1) inhibitors (4a) to combat resistance. Compound 4a was found to possess dual inhibitory capabilities in-vitro. Cytotoxic potential of 4a was found to be significantly higher than parent compound in 2D as well as 3D cancer cell models. Probable binding modes of 4a with TopoI and HDAC1 active sites were examined by molecular modelling.
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    Molecular phylogeography of Ficus benghalensis Linnaeus using nrDNA ITS 1, cpDNA trnL and cpDNA rps16 from the Indian subcontinent
    (Indian Academy of Sciences, 2019) Sharma S.; Mehra R.; Bast F.
    Ficus benghalensis Linnaeus (Moraceae) is the national tree of India and is well known for its pharmacolo-gical properties. The present study was aimed to determine the genetic diversity of F. benghalensis from the Indian subcontinent using sequence-based multi-locus phylogeography. A total of 20 geograph-ical isolates were collected from different regions, cov-ering major parts of its species range within the country. Sequence data from nuclear-encoded internal transcribed spacer region (ITS1), plastid-encoded trnL-F spacer region (trnL) and ribosomal intron re-gion (rps16) were generated. The trnL-based maxi-mum likelihood phylogram revealed the existence of two haplotypes, whereas ITS1 and rps16-based maxi-mum likelihood analysis did not reveal much variation for this species distributed in the Indian subcontinent. These results depict long-distance random gene flow across the subcontinent, and support the post-glacial population contraction events. To validate the impact of palaeo-historic climatic events on current geo-graphic and genetic distribution, species distribution modelling-coupled phylogeography is suggested.