Mini Reviews in Medicinal Chemistry - Volume 22, Issue 7, 2022

Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathways and the realization of alkaloids as cancer prevention drugs by targeting signal pathways remains.

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

Chromones are the class of secondary metabolites that broadly occur in the plant kingdom in a noticeable quantity. This rigid bicyclic system has been categorized “as privileged scaffolds in compounds” in medicinal chemistry. Their wide biological responses have made them an important moiety in a drug discovery program. This review provides updates on the various methods of synthesis of chromones and biological applications in medicinal chemistry. Various synthetic strategies for the construction of chromones include readily available phenols, salicylic acid and its derivatives, ynones, chalcones, enaminones, and 2-hydroxyarylalkylketones as starting materials. Synthesis of chromones by using metal, metal-free, nanomaterials and different other catalysts is herein included. Details of diverse biological activities of chromone derviatives, such as anti-cancer, antimicrobial, anti-viral, anti-inflammatory, antioxidant, as Monoamine Oxidase-B (MAO-B) inhibitors, anti- Alzheimer’s agents, anti-diabetic agents, having antihistaminic potential, and acting as antiplatelet agents, are discussed.

Background: Tuberculosis (TB) is an acute or chronic infectious disease caused by several species of Mycobacterium, collectively called tubercle bacilli or Mycobacterium tuberculosis complex. Around 10 million people get sick with tuberculosis (TB) each year. TB is the second leading cause of death today after HIV/AIDS. A serious problem in the context of MDR-TB is the extensively drug-resistant TB, which is an important reason for the restricted chemotherapy in TB. Therefore, there is a need to explore new antitubercular (anti-TB) agents. Coumarin is an oxygencontaining heterocyclic compound and can be widely found in many natural products, and many of them display diverse biological activities. The wide spectrum of activities of coumarin molecules has intrigued the scientists to explore the natural coumarins and their synthetic derivatives for their potential as anti-TB drugs. Objective: The objective of this review is to emphasize important coumarin analogs with anti-TB activities and their structure-activity relationships (SAR) for designing better anti-TB agents. Method: Latest, authentic and published reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being thoroughly studied and analyzed. The structural requirements of coumarins as anti-TB drugs have also been studied. Result: Collection and compilation of reports on various synthetic and natural coumarin derivatives and their anti-TB activities are being performed. Conclusion: The study provides the latest report on coumarin derivatives synthesized as anti-TB agent and whether their activity depends on structural changes or not.

The information about the presence of free radicals in biological materials was given for the first time about 70 years ago. Since then, numerous scientific studies have been conducted and the science of free radicals was introduced. Today we know that free radicals are by-products of enzymatic reactions occurring in the organism. They are produced during endogenous processes such as cell respiration, phagocytosis, biosynthesis, catalysis, and biotransformation. They can also be produced by exogenous processes (radiation, sunlight, heavy metals, bacteria, fungi, protozoa, and viruses). The overproduction of free radicals affects the aging processes, Oxidative Stress (OS) and takes part in the pathogenesis of various diseases. Among them are cancer, rheumatoid arthritis, neurodegenerative diseases: Alzheimer and Parkinson, pulmonary diseases, atherosclerosis, and DNA damage. Compounds with antioxidant activity are very important nowadays because they allow organisms to keep a balance between the production of free radicals and the speed of their neutralization in the body. Next to the natural antioxidants (flavonoids, carotenoids, vitamins, etc.), synthetic ones are also of great importance. Among synthetic compounds with antioxidant activity are 1,2,4-triazoles and their derivatives. 1,2,4-Triazoles are heterocyclic compounds with three nitrogen atoms. Due to a broad spectrum of biological activities, these derivatives have been of interest to scientists for many years. Some of them are also used as drugs. The finding of new synthetic compounds with antioxidant features in the triazole group has become an important problem of medicinal chemistry.