Mini Reviews in Medicinal Chemistry - Volume 21, Issue 8, 2021

Genus Pongamia and Derris belong to the Leguminosae family and are reported synonymously in literature. Although many compounds have been isolated from different plant parts but seed oil is known to produce non-edible medicinally important furanoflavonoids. The seed oil, commonly known as Karanj oil in Ayurvedic and Siddha traditional systems of medicine, is reported for the treatment of various skin infections and psoriasis. Several phytopharmacological investigations have proved the medicinal potential of furanoflavonoids in the skin and other disorders. Not only furanoflavonoids but several other important phenolic constituents such as chalcones, dibenzoylmethanes, aurones, isoflavones, flavanone dihydroflavonol, flavans, pterocarpans, rotenoids, coumarins, coumestans, stilbenoids and peltygynoids and their glycosides have been reported for different biological activities including antihyperglycemic, anti-inflammatory, anticancer, insecticidal, anti-alzheimer’s, gastro protective, antifungal, antibacterial, etc. In the present review, the phytochemistry and pharmacological activities of the genera Pongamia and Derris have been summarized.

The recent emergence of novel, pathogenic COVID-19 disease associated with SARSCoV- 2 virus in China and its rapid national and international spread pose a global health emergency. The development of a new drug is tedious and may take decades to develop and involve multiple steps like the development of prototypes and phase I to III human trials, which involve the study on small to large populations to examine the safety and side effects associated with the drug under trials. Due to continous increase in the number of confirmed cases and deaths, there is an urgent need to develop a drug that is effective to kill the SARS-CoV-2 virus with fewer side effects to the human body. Therefore, this review focus on the latest advances in the development for the treatment of COVID-19 disease associated with SARS-CoV-2 with repositioning of already marketed drug with small molecules, as well as Chinese traditional medicines with established safety and efficacy which are being used for different therapeutic uses.

As the world's population is aging, Alzheimer’s disease (AD) has become a big concern since AD has started affecting younger people and the population of AD patients is increasing worldwide. It has been revealed that the neuropathological hallmarks of AD are typically characterized by the presence of neurotoxic extracellular amyloid plaques in the brain, which are surrounded by tangles of neuronal fibers. However, the causes of AD have not been completely understood yet. Currently, there is no drug to effectively prevent AD or to completely reserve the symptoms in the patients. This article reviews the pathological features associated with AD, the recent progress in research on the drug development to treat AD, especially on the discovery of natural product derivatives to inhibit Aβ peptide aggregation as well as the design and synthesis of Aβ peptide aggregation inhibitors to treat AD.

Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have a distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for the treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structure-activity relationships, ligand-protein interactions, and in vitro and in vivo activity. Additionally, challenges, as well as opportunities, are also presented.

The novel coronavirus disease-19 (COVID-19) is a global pandemic that emerged from Wuhan, China, and has spread all around the world, affecting 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 updates of August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine exists. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID- 19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in clinical uses or studies on COVID-19 and also focuses on the mode of action of drugs being repositioned against COVID-19.

Heterocyclic compounds and their derivatives gained more attention due to their valuable biological and pharmacological properties. Benzothiazole is a heterocyclic structure containing a bicyclic ring system with a large panel of applications. The benzothiazole is present in many new products undergoing research hoping that it possesses various biological activities. Epilepsy is a diverse group of diseases marked by neuronal excitability and hypersynchronous neuronal activity of motor, sensory or autonomic events with or without loss of consciousness. Presently, many antiepileptic drugs like lamotrigine, stiripentol tiagabine, pregabalin, felbamate, and topiramate are available and effective towards 60-80% of patients only, along with undesirable side effects, such as hepatotoxicity, gastrointestinal disturbance, drowsiness, gingival hyperplasia, and hirsutism. Thus, many attempts are still on-going to develop antiepileptic drugs with a safer profile. This review is mainly focused on the compilation of reported scientific literature data in the recent one-decade on the anticonvulsant activity of benzothiazole compounds.

In drug discovery, in silico methods have become a very important part of the process. These approaches impact the entire development process by discovering and identifying new target proteins as well as designing potential ligands with a significant reduction of time and cost. Furthermore, in silico approaches are also preferred because of reduction in the experimental use of animals as; in vivo testing for safer drug design and repositioning of known drugs. Novel software-based discovery and development such as direct/indirect drug design, molecular modelling, docking, screening, drug-receptor interaction, and molecular simulation studies are very important tools for the predictions of ligand-target interaction pattern, pharmacodynamics as well as pharmacokinetic properties of ligands. On the other part, the computational approaches can be numerous, requiring interdisciplinary studies and the application of advanced computer technology to design effective and commercially feasible drugs. This review mainly focuses on the various databases and software used in drug design and development to speed up the process.