Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA. Electronic address:
Published: February 2022
AI Article Synopsis
Article Abstract
Polypharmacology is a concept where a molecule can interact with two or more targets simultaneously. It offers many advantages as compared to the conventional single-targeting molecules. A multi-targeting drug is much more efficacious due to its cumulative efficacy at all of its individual targets making it much more effective in complex and multifactorial diseases like cancer, where multiple proteins and pathways are involved in the onset and development of the disease. For a molecule to be polypharmacologic in nature, it needs to possess promiscuity which is the ability to interact with multiple targets; and at the same time avoid binding to antitargets which would otherwise result in off-target adverse effects. There are certain structural features and physicochemical properties which when present would help researchers to predict if the designed molecule would possess promiscuity or not. Promiscuity can also be identified via advanced state-of-the-art computational methods. In this review, we also elaborate on the methods by which one can intentionally incorporate promiscuity in their molecules and make them polypharmacologic. The polypharmacology paradigm of "one drug-multiple targets" has numerous applications especially in drug repurposing where an already established drug is redeveloped for a new indication. Though designing a polypharmacological drug is much more difficult than designing a single-targeting drug, with the current technologies and information regarding different diseases and chemical functional groups, it is plausible for researchers to intentionally design a polypharmacological drug and unlock its advantages.
Inhaled β2 agonists form the first-line treatment for bronchial asthma due to their superior bronchodilator effects. In our previous studies, we have identified a significant association of Thr164Ile (T164I) polymorphism (C491T, rs1800088) in the β2 adrenergic receptor (β2AR) with refractoriness to β2 agonists like salbutamol. Utilizing molecular modeling approaches, we have demonstrated the suboptimal binding of salbutamol as a plausible rationale behind the refractoriness observed in asthmatics.
Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Electronic address:
The human gastrointestinal tract is a competitive environment inhabited by dense polymicrobial communities. Bacteroides, a genus of Gram-negative anaerobes, are prominent members of this ecological niche. Bacteroides spp.
Coronavirus disease 2019 (COVID-19) is caused by a new, highly pathogenic severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects human cells through its transmembrane spike (S) glycoprotein. The receptor-binding domain (RBD) of the S protein interacts with the angiotensin-converting enzyme II (ACE2) receptor of the host cells. Therefore, pharmacological targeting of this interaction might prevent infection or spread of the virus.
Angelica decursiva, an important traditional medicinal plant, possesses a unique pharmacological activity. Its principal active ingredients are coumarins, including scopoletin, bergapten, and imperatorin. However, the enzymes catalyzing the critical step of coumarins biosynthesis pathway remain unidentified.
Amaryllidaceae alkaloids (AAs) are complex plant secondary metabolites possessing a wide range of biological activities. 4'-O-methylnorbelladine (4OMN) is the branchpoint intermediate for the entire AAs, and was the last common intermediate before AA pathway branches diverge. The cyclization of 4OMN by C-C oxidative coupling, which can afford ', ', and ' scaffold, was catalyzed by cytochrome P450 96T (CYP96T) family enzymes.
