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1.
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.

2.
Rasayan Journal of Chemistry ; 14(4):2639-2644, 2021.
Article in English | Scopus | ID: covidwho-1614546

ABSTRACT

Remdesivir (RMDSVR) is a pro-drug of an ATP analog, with antiviral activity against RNA viruses. In 2016 RMDSVR is used in the treatment of Ebola and 2017 RMDSVR was tested against SARS-CoV-2. The HPLC analysis was performed on the Agilent 1100 series HPLC with Quaternary G1311 A pump, ChromosilC18 column (250 X 4.6 mm, 5μ) column, with a mixture of Acetonitrile, Methanol and 0.1% OPA in the ratio of 65:30:5 (v/v) as the mobile phase, at 0.8 mL/min flow rate and UV detection at 272 nm. Abacavir (ABVR) is considered an internal standard and the retention time was observed at 6.0 min and 9.1 min for RMDSVR and ABVR respectively. The calibration curve was obtained linearly in the concentration range of 10-70 ng/mL. the method was validated and all the validated parameters were within the acceptable limit confirms that the method is suitable for the analysis of RMDSVR in spiked human plasma. © 2021, Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma. All rights reserved.

3.
J Mol Struct ; 1230: 129868, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1164239

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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