:
The COVID-19 pandemic continues to wreak havoc worldwide due to the lack of risk assessment, rapid spreading ability, and propensity to precipitate severe disease in comorbid conditions. In an attempt to fulfill the demand for
prophylactic and treatment measures to intercept the ongoing outbreak, the drug development process is facing several obstacles and renaissance in clinical trials, including vaccines, antivirals, immunomodulators, plasma therapy, and traditional
medicines. This review outlines the overview of SARS-CoV-2 infection, significant recent findings, and ongoing clinical
trials concerning current and future therapeutic interventions for the management of advancing pandemic of the century.
A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a–f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g–k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.
Background:
Adenosine mediates various physiological and pathological conditions by acting on its
four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide
range of biological activities. Thus, its modulation is implicated in various disorders like Parkinson’s disease,
asthma, cardiovascular disorders, cancer etc. Hence these receptors have become an interesting target for the
researchers to develop potential therapeutic agents. Number of molecules were designed and developed in the
past few years and evaluated for their efficacy in various disease conditions.
Objective:
The main objective is to provide an overview of new chemical entities which have crossed preclinical
studies and reached clinical trials stage following their current status and future prospective.
Methods:
In this review we discuss current status of the drug candidates which have undergone clinical trials and
their prospects.
Results:
Many chemical entities targeting various subtypes of P1 receptors are patented; twenty of them have
crossed preclinical studies and reached clinical trials stage. Two of them viz adenosine and regadenoson are approved
by the Food and Drug Administration.
Conclusion:
This review is an attempt to highlight the current status, progress and probable future of P1 receptor
ligands which are under clinical trials as promising novel therapeutic agents and the direction in which research
should proceed with a view to come out with novel therapeutic agents.
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