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Pyrrolo[2,3-b]quinoxalines in attenuating cytokine storm in COVID-19: their sonochemical synthesis and in silico / in vitro assessment.
Chemboli, Raviteja; Kapavarapu, Ravikumar; Deepti, K; Prasad, K R S; Reddy, Alugubelli Gopi; Kumar, A V D Nagendra; Rao, Mandava Venkata Basaveswara; Pal, Manojit.
  • Chemboli R; Department of Chemistry, Koneru Lakshmaiah Education Foundation, Greenfields, Vaddeswaram, Guntur, Andhra Pradesh 522 502, India.
  • Kapavarapu R; Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500046, India.
  • Deepti K; Department of Chemistry, Koneru Lakshmaiah Education Foundation, Greenfields, Vaddeswaram, Guntur, Andhra Pradesh 522 502, India.
  • Prasad KRS; Department of Chemistry, Koneru Lakshmaiah Education Foundation, Greenfields, Vaddeswaram, Guntur, Andhra Pradesh 522 502, India.
  • Reddy AG; Department of Pharmacy, SANA College of Pharmacy, Kodad, Telangana 508206, India.
  • Kumar AVDN; Department of Chemistry, GIS, GITAM Deemed to be University, Visakhapatnam, Andhra Pradesh 530 045, India.
  • Rao MVB; Department of Chemistry, Krishna University, Krishna District, Andhra Pradesh, India.
  • Pal M; Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500046, India.
J Mol Struct ; 1230: 129868, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1734825
ABSTRACT
In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-substituted pyrrolo[2,3-b]quinoxalines for this purpose because of their potential inhibitory properties of PDE-4 / TNF-α. Moreover, several of these compounds appeared to be promising in silico when assessed for their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. A rapid and one-pot synthesis of this class of molecules was achieved via the Cu-catalyzed coupling-cyclization-desulfinylation of 3-alkynyl-2-chloroquinoxalines with t-butyl sulfinamide as the ammonia surrogate under ultrasound irradiation. Most of these compounds showed good to significant inhibition of TNF-α in vitro establishing a SAR (Structure Activity Relationship) within the series. One compound e.g. 3i was identified as a promising hit for which the desirable ADME and acceptable toxicity profile was predicted in silico.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: J Mol Struct Year: 2021 Document Type: Article Affiliation country: J.molstruc.2020.129868

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: J Mol Struct Year: 2021 Document Type: Article Affiliation country: J.molstruc.2020.129868