Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents.

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, ß-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future.

Comprehensive coverage on anti-mycobacterial endeavour reported during 2022.

TB being one of the deadliest diseases and second most common infectious cause of deaths, poses the severe threat to global health. The extended duration of therapy owing to resistance and its upsurge in immune-compromised patients have been the driving force for the development of novel of anti-TB scaffolds. Recently, we have compiled the account of anti-mycobacterial scaffolds published during 2015-2020 and updated them in 2021. The present work involves the insights on the anti-mycobacterial scaffolds reported in 2022 with their mechanism of action, structure activity relationships, along with the key perceptions for the design of newer anti-TB agents for the broader interests of medicinal chemists.

A Quinquennial Review on Recent Advancements and Developments in Search of Anti-malarial Agents.

Malaria has been a major parasitic disease in tropical and subtropical regions and is estimated to kill between one and two million people (mainly children) every year. Novel anti-malarial agents are urgently needed to combat the malarial parasites enduring resistance to the current medications, leading to increased morbidity and mortality. The heterocycles, holding a prominent position in chemistry and found in both natural and synthetic sources, have shown several biological activities including anti-malarial activity. Towards this goal, several research groups have reported the design and development of novel and potential anti-malarial agents like artemisinin, benzimidazole, benzothiazole, chalcone, cyclopeptide, fosmidomycin, furan, indole oxadiazole, 2-oxindoles, peroxides, pyrazole, pyrazolines, pyridines, pyrimidine, pyrrolidine, quinazoline, quinazolinone, quinolone, quinoline, thiazole, triazole and other scaffolds acting against newly emerging anti-malarial targets. The present work reports the complete quinquennial coverage of anti-malarial agents reported during 2016-2020 with a view of providing the merits and demerits of reported anti-malarial scaffolds, structure-activity relationship, along with their in vitro/ in vivo/ in silico profiles to the medicinal chemists working in the field of design and discovery of novel anti-malarial agents.

Recent Advances in N-Heterocycles for COVID-19 Treatment - A Mini Review.

Severe emergencies occurred across the globe, beginning with the outbreak of SARSCoV in 2002, followed by MERS-CoV in 2012. In December 2019, an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China as the agent responsible for the recent COVID-19 pandemic outbreak. The virus rapidly spread throughout the world due to its high transmissibility, leading to enormous health problems and complexities. The COVID-19 pandemic has affected public health, the weak persons were severely affected by this virus. To stop the disease from spreading further, effective remedies are the need of the hour. Although SARS-CoV-2 vaccination campaigns are being carried out all over the globe, several new SARS-CoV-2 variants have emerged, and each has caused a wave of infections, highlighting an urgent need for therapeutics targeting SARS-CoV-2. Heterocyclic compounds have been explored extensively for a very long time for their biological activities, namely, anti-inflammatory, antimalarial, antitubercular, anticancer, antiviral, antimicrobial, antidiabetic, and many more bio-activities. Through this review, the author has tried to report the heterocyclic compounds synthesized all over the world over the last 2 years to fight against the SARS CoV-2 coronaviruses. The heterocyclic motifs mentioned in the review can serve as important resources for the development of COVID-19 treatment methods.

Strategies in synthetic design and structure-activity relationship studies of novel heterocyclic scaffolds as aldose reductase-2 inhibitors.

Heterocyclic scaffolds of natural as well as synthetic origin provide almost all categories of drugs exhibiting a wide range of pharmacological activities, such as antibiotics, antidiabetic and anticancer agents, and so on. Under normal homeostasis, aldose reductase 2 (ALR2) regulates vital metabolic functions; however, in pathological conditions like diabetes, ALR2 is unable to function and leads to secondary diabetic complications. ALR2 inhibitors are a novel target for the treatment of retinopathy (cataract) influenced by diabetes. Epalrestat (stat), an ALR2 inhibitor, is the only drug candidate that was approved in the last four decades; the other drugs from the stat class were retracted after clinical trial studies due to untoward iatrogenic effects. The present study summarizes the recent development (2014 and onwards) of this pharmacologically active ALR2 heterocyclic scaffold and illustrates the rationale behind the design, structure-activity relationships, and biological studies performed on these molecules. The aim of the current review is to pave a straight path for medicinal chemists and chemical biologists, and, in general, to the drug discovery scientists to facilitate the synthesis and development of novel ALR2 inhibitors that may serve as lead molecules for the treatment of diseases related to the ALR2 enzyme.

Seeking heterocyclic scaffolds as antivirals against dengue virus.

Dengue is one of the most typical viral infection categorized in the Neglected Tropical Diseases (NTDs). It is transmitted via the female Aedes aegypti mosquito to humans and majorly puts risk to the lives of more than half of the world. Recent advancements in medicinal chemistry have led to the design and development of numerous potential heterocyclic scaffolds as antiviral drug candidates for the inhibition of the dengue virus (DENV). Thus, in this review, we have discussed the significance of inhibitory and antiviral activities of nitrogen, oxygen, and mixed (nitrogen-sulfur and nitrogen-oxygen) heterocyclic scaffolds that are published in the last seven years (2016-2022). Furthermore, we have also discussed the probable mechanisms of action and the diverse structure-activity relationships (SARs) of the heterocyclic scaffolds. In addition, this review has elaborately outlined the mechanism of viral infection and the life cycle of DENV in the host cells. The wide set of heterocycles and their SARs will aid in the development of pharmaceuticals that will allow the researchers to synthesize the promising anti-dengue drug candidate in the future.

Current Perspective of Synthesis of Medicinally Relevant Benzothiazole based Molecules: Potential for Antimicrobial and Anti-Inflammatory Activities.

The therapeutic potential of the majority of the marketed drugs is due to the presence of a heterocyclic nucleus, which constitutes a huge role in the field of medicinal chemistry. These heterocyclic scaffolds could act as a template in order to design potential therapeutic agents against several diseases. Benzothiazole scaffold is one of the influential heteroaromatic rings in the field of medicinal chemistry owing to its extensive pharmacological features. Herein, we have focused on the synthesis of benzothiazole-based medicinal molecules, which possess antimicrobial and anti-inflammatory activities. This review covers a systematic description of synthetic routes for biologically relevant benzothiazole derivatives in the last five years. The main aim of this study is to show the diversification of benzothiazole-based molecules into their pharmacologically more active derivatives. This review's synthetic protocols include metal-free, metal-catalyzed, and metal precursor azo dyes strategies for the development of benzothiazole derived bioactive compounds. The discussion under the various headings covers synthetic schemes and biological activities of the most potent molecules in the form of minimum inhibitory concentration.

Dual Monoamine Oxidase and Cholinesterase Inhibitors with Different Heterocyclic Scaffolds.

For the last two decades, there has been research interest on the design of molecules possessing dual inhibitory potential on cholinesterase and monoamine oxidase enzymes, particularly for the treatment of two major neurodegenerative diseases, Alzheimer's Disease (AD) and Parkinson's disease (PD). Many compounds have been synthesized for this purpose, and some of them have been shown to display activities comparable or superior to the activities of current drugs used for the treatment of AD and PD. Within the concept of this review study, we have aimed to present the current drugs used for the treatment of AD and PD, their mechanism of action, the discussion behind the theory of designing dual inhibitor agents, and the presentation of the most active compounds with diverse heterocyclic scaffolds displayed in research studies published in the recent period.

Role of heterocyclic compounds in SARS and SARS CoV-2 pandemic.

Coronaviruses have led to severe emergencies in the world since the outbreak of SARS CoV in 2002, followed by MERS CoV in 2012. SARS CoV-2, the novel pandemic caused by coronaviruses that began in December 2019 in China has led to a total of 24,066,076 confirmed cases and a death toll of 823,572 as reported by World Health Organisation on 26 August 2020, spreading to 213 countries and territories. However, there are still no vaccines or medications available till date against SARS coronaviruses which is an urgent requirement to control the current pandemic like situations. Since many decades, heterocyclic scaffolds have been explored exhaustively for their anticancer, antimalarial, anti-inflammatory, antitubercular, antimicrobial, antidiabetic, antiviral and many more treatment capabilities. Therefore, through this review, we have tried to emphasize on the anticipated role of heterocyclic scaffolds in the design and discovery of the much-awaited anti-SARS CoV-2 therapy, by exploring the research articles depicting different heterocyclic moieties as targeting SARS, MERS and SARS CoV-2 coronaviruses. The heterocyclic motifs mentioned in the review can serve as crucial resources for the development of SARS coronaviruses treatment strategies.

Microwave Assisted Synthesis of Biorelevant Benzazoles.

The benzazole scaffolds are present in various therapeutic agents and have been recognized as the essential pharmacophore for diverse biological activities. These have generated interest and necessity to develop efficient synthetic methods of these privileged classes of compounds to generate new therapeutic leads for various diseases. The biological activities of the benzazoles and efforts towards their synthesis have been summarized in a few review articles. In view of these, the aim of this review is to provide an account of the developments that have taken place in the synthesis of biorelevant benzazoles under microwave irradiation as the application of microwave heating has long been recognized as a green chemistry tool for speedy generation of synthetic targets. Attention has been focused to those literature reports wherein the use of microwave irradiation is the key step in the formation of the heterocyclic ring system or in functionalization of the benzazole ring system to generate the essential pharmacophoric feature. The convenient and economic way to synthesize these privileged class of heterocycles through the use of microwave irradiation that would be beneficial for the drug discovery scientist to synthesize biologically active benzazoles and provide access to wide range of reactions for the synthesis of benzazoles constitute the theme of this review. Examples have been drawn wherein the use of microwave heating offers distinct advantage in terms of improved product yields and reduction of reaction time as compared to those observed for the synthesis under conventional heating.