Multi-target Polypharmacology of 4-aminoquinoline Compounds against Malaria, Tuberculosis and Cancer.

BACKGROUND: Polypharmacology means drugs having interactions with multiple targets of a unique disease or many disease pathways. This concept has been greatly appreciated against complex diseases, such as oncology, CNS disorders, and anti-infectives. METHODS: The integration of diverse compounds available on public databases initiates polypharmacological drug discovery research. Immunocompromised patients may suffer from complex diseases. Multiple-component drug formulations may produce side effects and resistance issues due to unintended drug-target interactions. RESULTS: Polypharmacology remains a novel avenue to propose a more effective and less toxic treatment. The 4-amino quinoline scaffold has become an important construction motif for the development of new drugs against lifestyle diseases like cancer and infectious diseases like tuberculosis and malaria. CONCLUSION: The present study is an attempt to explore the polypharmacological effects of 4- aminoquinoline drugs to combat malaria, cancer, and tuberculosis.

Repurposing of Chemotherapeutics to Combat COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel strain of SARS coronavirus. The COVID-19 disease caused by this virus was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 mainly spreads through droplets sprayed by coughs or sneezes of the infected to a healthy person within the vicinity of 6 feet. It also spreads through asymptomatic carriers and has negative impact on the global economy, security and lives of people since 2019. Numerous lives have been lost to this viral infection; hence there is an emergency to build up a potent measure to combat SARS-CoV-2. In view of the non-availability of any drugs or vaccines at the time of its eruption, the existing antivirals, antibacterials, antimalarials, mucolytic agents and antipyretic paracetamol were used to treat the COVID-19 patients. Still there are no specific small molecule chemotherapeutics available to combat COVID-19 except for a few vaccines approved for emergency use only. Thus, the repurposing of chemotherapeutics with the potential to treat COVID-19 infected people is being used. The antiviral activity for COVID-19 and biochemical mechanisms of the repurposed drugs are being explored by the biological assay screening and structure-based in silico docking simulations. The present study describes the various US-FDA approved chemotherapeutics repositioned to combat COVID-19 along with their screening for biological activity, pharmacokinetic and pharmacodynamic evaluation.