Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first reported in Wuhan, China, in December 2019. Since then, the virus has stretched its grip to almost all the countries in the world, affecting millions of people and causing enormous casualties. The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2019. As of June 12, 2020, almost 7.30 million people have already been infected globally, with 413,000 reported casualties. In the United States alone, 2.06 million people have been infected and 115,000 have succumbed to this pandemic. A multipronged approach has been launched toward combating this pandemic, with the main focus on exhaustive screening, developing efficacious therapies, and vaccines for long-term immunity. Several pharmaceutical companies in collaboration with various academic institutions and governmental organizations have started investigating new therapeutics and repurposing approved drugs so as to find fast and affordable treatments against this disease. The present communication is aimed at highlighting the efforts that are currently underway to treat or prevent SARS-CoV-2 infection, with details on the science, clinical status, and timeline for selected investigational drugs and vaccines. This article is going to be of immense help to the scientific community and researchers as it brings forth all the necessary clinical information of the most-talked-about therapeutics against SARS-CoV-2. All the details pertaining to the clinical status of each therapeutic candidate have been updated as of June 12, 2020.

Synthesis, 17α-hydroxylase-C17,20-lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives.

BACKGROUND: The potential of steroids for development into lead pharmacological molecules lies in the regulation of a variety of biological processes by these molecules and also because of these being a fundamental class of signaling molecules. Steroid based scaffolds have been extensively used as active pharmaceutical agents for the treatment of various diseases including the deadly disease of cancer which despite the recent advances in the early diagnosis, prevention and therapy, remains a clinical challenge affecting millions of people world over and is one of the leading causes of death. It thus warrants the development of new drugs against this dreadful disease through exploitation of emerging molecularly defined targets. METHODS: The present study explores the effect of novel steroidal pyrazolines as presumed inhibitors of 5α- reductase (5AR) and 17α-hydroxylase-C17,20-lyase as a target for treatment of prostate cancer. A series of 1,5- diaryl pyrazoline pregnenolones were synthesized and screened for 5α-reductase inhibitory activities. Synthesis of the analogs is multistep and proceeds in good overall yields. The key step in the synthesis of 1,5- disubstituted pyrazolinyl pregnenolones is the heterocyclization of bezylidine derivatives (3) in presence of phenylhydrazines (4) through the initial formation of the phenylhydrazones, which undergo concomitant cyclization to generate the stable pyrazoline derivatives. RESULTS: All the synthesised D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were screened for prostate cancer cell inhibitory, 5α-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active. Further, compounds 5g and 5h were found to have moderate 17α-hydroxylase-C17,20-lyase inhibitory activities. CONCLUSION: A series of D-ring 1,5-disubstituted pyrazolinyl pregnenolone derivatives (5a-l) were synthesized and screened for their prostate cancer cell inhibitory, 5a-reductase and 17α-hydroxylase-C17,20-lyase inhibitory activity. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 5c, 5e, 5g and 5l were found to be the most active whereas compounds 5g and 5h were found to have moderate 17α- hydroxylase-C17,20-lyase inhibitory activities.

Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors: synthesis and biological evaluation.

Taking pregnenolone as the starting material, two series of pyrazolinyl and pyrazolyl pregnenolones were synthesized through different routes. The synthesis of the analogs of both series is multistep and proceeds in good overall yields. While the key step in the synthesis of pyrazolinyl pregnenolones is the heterocyclization of benzylidine derivatives (3) in presence of hydrazine hydrate, it is the condensation of 3ß-hydroxy-21-hydroxymethylidenepregn-5-en-3ß-ol-20-one (5) with phenylhydrazine in the synthesis of pyrazolyl derivatives. Compounds of both the series were tested for their 5α-reductase inhibitory activities. Amongst all the compounds screened for their 5α-reductase inhibitory activities, compound 4b, 4c and 6b were found to be the most active.

Benzylidine pregnenolones and their oximes as potential anticancer agents: synthesis and biological evaluation.

The present study reveals the anticancer activity of benzylidine pregnenolones and their oxime derivatives. The synthesis of the analogs of both series is very simple and involves aldol condensation in the first step followed by nucleophillic addition of hydroxylamine across carbonyl in the second step. Quantitative yields of more than 80% are obtained in both the steps. All the compounds were tested for their cytotoxic activities against a panel of six human cancer cell lines. Amongst all the compounds of both the series screened for their cytotoxic activity, compound 3e, 3f and 4e are very potent especially against HCT-15 and MCF-7 cancer cell lines.

Antimicrobial studies of unsymmetrical bis-1,2,3-triazoles.

Aryl azides were treated with allenylmagnesium bromide to generate 1,5-disubstituted butynyl 1,2,3-triazoles in a domino fashion, which upon Cu(I) catalyzed 1,3-dipolar cycloaddition with aryl azides afforded novel bis-1,2,3-triazoles in quantitative yields. The final products were analyzed for their antimicrobial activities against a panel of bacterial and fungal strains which revealed the products to be potent antimicrobials.

D-ring substituted 1,2,3-triazolyl 20-keto pregnenanes as potential anticancer agents: Synthesis and biological evaluation.

A facile synthesis of 21-triazolyl derivatives of pregnenolone and their potential antitumour activity is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to 21-bromo pregnenolone and finally the one-pot, two-step in situ conversion of the bromo derivative to the 21-triazolyl pregnenolone using the 'click chemistry' approach. These derivatives were screened for their anticancer activity against seven human cancer cell lines. The compounds especially 5a, 5b, 5c, 5e, 5g and 5h exhibited significant anticancer activity with compound 5e as the most active in this study.