School Of Basic And Applied Sciences

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Subject: search.filters.subject.Molecular modelling

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    Selection of active antiviral compounds against COVID-19 disease targeting coronavirus endoribonuclease nendou/NSP15 via ligand-based virtual screening and molecular docking
    (Bentham Science Publishers, 2020-12-15T00:00:00) Joshi, Gaurav; Poduri, Ramarao
    Background: The rapid spread of SARS-CoV-2 has caused havoc and panic among individuals, which has further worsened due to the unavailability of a proven drug(s) regime. Objective: The current work involves drug repurposing from the pool of USFDA approved drugs involving in silico virtual screening technique against COVID-19. Materials and Methods: Methodology involves virtual screening of 8548 FDA approved drugs against target protein endoribonuclease NendoU (Nsp15) (PDB ID: 6VWW). Result: Virtual screening-based analysis enabled us to identify four drugs, Eprosartan, Inarigivir soproxil, Foretinib, and DB01813 that could plausibly target Nsp15 against COVID-19 disease. Conclusion: The work offers the scope to corroborate the findings via in vitro and in vivo techniques to identify the potential of selected leads against COVID-19. The outcome may also help in tracing their molecular mechanism(s) in addition to their development at the clinical level in the future. � 2021 Bentham Science Publishers.
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    Designing specific inhibitors against dihydrofolate reductase of W. bancrofti towards drug discovery for lymphatic filariasis
    (Springer, 2022-03-15T00:00:00) Sureshan, Muthusamy; Rajamanikandan, Sundarraj; Srimari, Srikanth; Prabhu, Dhamodharan; Jeyakanthan, Jeyaraman; Saraboji, Kadhirvel
    Lymphatic filariasis (LF) is one among the leading neglected diseases caused by mosquitoe-borne parasite Wuchereria bancrofti to humans. Though drugs are available for the treatment of LF, all of which are not effective in all stages and moreover majority of these drugs have been reported with resistance. There is a need for effective new drugs which affect the parasite irrespective of its lifecycle and counter the drug resistance mechanisms. In the present study, we have explored the key enzyme dihydrofolate reductase (DHFR) as the potential target for developing drugs against LF. We have modelled dihydrofolate reductase structure and analysed its stability through the 200�ns simulation studies. Computer-assisted screening method found five non-toxic potent hit molecules with a docking score of ? 13.86 to ? 13.54�kcal/mol. Interestingly, we observed that the identified hit molecules are more specific to W. bancrofti DHFR than human DHFR due to electrostatic charge variations in the binding cavity. Higher specificity could increase the therapeutic efficacy and also minimize cross-reactivity with human targets. We have also found that the identified hit molecules have better glide score and energy than the reported DHFR inhibitors of W. bancrofti. Better score and energy values depict that the identified hit molecules could inhibit the DHFR activity efficiently. The DFT analysis predicted the regions in the hit molecules with higher probability of chemical reactivity and also potential sites to enhance the binding efficiency. Our findings provide new scaffolds for the development of DHFR inhibitors, which can be efficiently formulated to treat LF. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    A review on quinoline derived scaffolds as anti-HIV agents
    (Bentham Science Publishers, 2019) Chokkar N.; Kalra S.; Chauhan M.; Kumar R.
    After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.
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    Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors
    (Academic Press Inc., 2019) Ansari, A.J; Joshi, G; Yadav, U.P; Maurya, A.K; Agnihotri, V.K; Kalra, S; Kumar, R; Singh, S; Sawant, D.M.
    A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 < 2.5 ?M) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.
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    A review on quinoline derived scaffolds as Anti-HIV Agents.
    (Bentham Science, 2018) Chokkar, N.; Kalra, S; Chauhan, M; Kumar, Raj
    After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.