Mini Reviews in Medicinal Chemistry - Volume 22, Issue 1, 2022

Abstract: Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors and the ligand-activated intracellular transcription factors that are known to play a key role in physiological processes such as cell metabolism, proliferation, differentiation, tissue remodeling, inflammation, and atherosclerosis. However, in the past two decades, many reports claim that PPARs also play an imperious role as a tumor suppressor. PPAR- gamma (PPARγ), one of the best-known from the family of PPARs, is known to express in colon, breast, bladder, lung, and prostate cancer cells. Its function in tumour cells includes the modulation of several pathways involved in multiplication and apoptosis. The ligands of PPARγ act by PPARγ dependent as well as independent pathways and are also found to regulate different inflammatory mediators and transcription factors in systemic inflammation and in tumor microenvironment. Both synthetic and natural ligands that are known to activate PPARγ, suppress the tumor cell growth and multiplication through the regulation of inflammatory pathways, as found out from different functional assays and animal studies. Cancer and inflammation are interconnected processes that are now being targeted to achieve tumor suppression by decreasing the risks and burden posed by cancer cells. Therefore, PPARγ can serve as a promising target for development of clinical drug molecule attenuating the proliferation of cancer cells. In this perspective, this mini review highlights the PPARγ as a potential target for drug development aiming for anti-inflammatory and thereby suppressing tumors.

Background: For decades, the quinoxaline 1,4-di-N-oxide ring has been considered a privileged structure to develop new antibacterial, antitumoural, and antiprotozoal agents, among others; however, its mechanism of action is not clear. Objective: The main aim of this mini-review was to analyze the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives reported as antibacterial, antitumoural, and antiprotozoal agents. Results: Initially, the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives against bacteria, tumoural cell lines, and parasites have been described as nonspecific, but recently, the results against different organisms have shown that these compounds have an inhibitory action on specific targets such as trypanothione reductase, triosephosphate isomerase, and other essential enzymes. Conclusion: In summary, quinoxaline 1,4-di-N-oxide is a scaffold to develop new anti- Mycobacterium tuberculosis, antitumoural and antiprotozoal agents; however, understanding the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives in each microorganism could contribute to the development of new and more potent selective drugs.

Abstract: Staphylococcus aureus is a prominent human pathogen that causes nosocomial and community acquired infections. The accelerating emergence and prevalence of staphylococcal infections have grotesque health consequences which are mostly due to its anomalous capability to acquire drug resistance and scarcity of novel classes of antibacterials. Many combating therapies are centered on primary targets of S. aureus which are cell envelope, ribosomes and nucleic acids. This review describes various chemotherapeutic strategies for combating S. aureus infections including monotherapy, combination drug therapy, phage endolysin therapy, lysostaphins and antibacterial drones. Monotherapy has dwindled in due course of time, but combination therapy, endolysin therapy, lysostaphin and antibacterial drones are emerging alternatives which efficiently conquer the shortcomings of monotherapy. Combinations of more than one antibiotic agents or combination of adjuvant with antibiotics provide a synergistic approach to combat infections causing pathogenic strains. Phage endolysin therapy and lysostaphin are also presented as possible alternatives to conventional antibiotic therapies. Antibacterial Drones go a step further by specifically targeting the virulence genes in bacteria, giving them a certain advantage over existing antibacterial strategies. But the challenge remains on the better understanding of these strategies for executing and implementing them in the health sector. In this day and age, most of the S. aureus strains are resistant to an ample number of antibiotics, so there is an urgent need to overcome such multidrug-resistant strains for the welfare of our community.

Abstract: Alzheimer’s Disease (AD) is one of the most common neurodegenerative diseases with chronic, progressive, and irreversible characteristics, affecting nearly 50 million older adults worldwide. The pathogenesis of AD includes the formation of senile plaques, the abnormal aggregation of tau protein and the gradual degeneration and death of cerebral cortical cells. The main symptoms are memory loss, cognitive decline and behavioral disorders. Studies indicate that cannabidiol (CBD) possesses various pharmacological activities, including anti-inflammatory, anti-oxidation and neuroprotective activities. It has been suggested as a potential multi-target medicine for the treatment of AD. In this review, we aim to summarize the underlying mechanisms and protective effects of CBD on signaling pathways and central receptors involved in the pathogenesis of AD, including the endocannabinoid system (eCBs), the Transient receptor potential vanilloid type 1(TRPV1) receptor, and the Peroxisome Proliferator-Activated Receptor (PPAR) receptor.

Abstract: Inherited beta-thalassemia is caused by irregular production of hemoglobin through reducing beta-globin chains. It has been observed that increasing fetal hemoglobin (HbF) production improves symptoms in the patients; thus, it has been an operative approach to treat patients with betathalassemia. This review represents compounds with biological activities and pharmacological properties that can be useful in promoting the HBF level in β-thalassemia patients. Various natural products with different mechanisms of action can be helpful in this medication cure. Clinical trials were efficient in improving the signs of patients. Association of in vivo, and in vitro studies of HbF induction and γ-globin mRNA growth displays that in vitro experiments could be an indicator of the in vivo response. The current study resulted that; (a) HbF inducers can be grouped into several classes based on their chemical structures and mechanism of actions; (b) According to several clinical trials, wellknown drugs such as hydroxyurea and decitabine are useful HbF inducers. (c) The cellular biosensor K562 carrying genes under the control of the human γ-globin and β-globin gene promoters were applied during the researches. (d) New natural products and lead compounds were found based on various studies as HbF inducers.

Abstract: Globally, cancer is considered as the major leading cause in burdening the patient’s health care system globally. The growing threat of drug-resistant cancers renders an urgent need to develop more successful candidates for the anti-cancer therapy. In view of the outstanding pharmacological activities, Quinolone and its derivatives have attracted more attention towards drug designing and biological evaluation in the search for new drug molecules. The inspired researchers attempted efforts in order to discover the quinolone based analogs due to their wide range of biological activities. Due to immense pharmacological importance, distinct synthetic methods have been executed to attain new drug entities from quinolones and all the reported molecules have shown constructive anticancer activities. Some of the synthetic protocols like one pot synthesis, post-Ugi-transformation, catalysed based synthesis, enzyme-based synthesis and nano-catalyst based synthetic procedures are also discussed as recent advancements in the production of quinolone derivatives. In this review, recent synthetic approaches in the medicinal chemistry of quinolones and potent quinolone derivatives on the basis of structural activity relationship are outlined. Moreover, their major methods and modifications are discussed.

Abstract: The occurrence of the diabetes happens due to the irregular operation of glucose in the body, which is also known as glucose homeostasis, thus leading to metabolic changes in the body. The two stages whether hypoglycemia or hyperglycemia differentiates diabetes into various categories and brought new innovative management for the new routes of administration of these disease condition. Various bio-nanotechnologies which are coupled with nano particulates, polymers, Liposome, various gold plated and Solid Lipids Particulates regulate the transcellular transport, non specific cellular uptake, and paracellular transport, which leads to oral, transdermal, Pulmonary, buccal, Nasal, specific gene oriented administration to avoid the non patience compliance with the parental routes of administration. Phytochemicals have an emerging strategy for the future prospects of diabetes management.

Abstract: The search for new anticancer agents is considered a dynamic field of medicinal chemistry. In recent years, the synthesis of compounds with anticancer potential has increased and a large number of structurally varied compounds displaying potent anticancer activities have been published. Pyrazole is an important biologically active scaffold that possesses nearly all types of biological activities. The aim of this review is to collate literature work reported by researchers to provide an overview on in vivo and in vitro anticancer activities of pyrazole based derivatives among the diverse biological activities displayed by them and also to present recent efforts made on this heterocyclic moiety regarding anticancer activities. This review has been driven by the increasing number of publications on this issue, which have been reported in the literature since the end of the 20^th century (from 1995-to date).

Abstract: Background: Cancer is the first or second leading cause of premature death in 134 of 183 countries in the world. 1,3,4-Oxadiazoles are five membered heterocyclic rings containing nitrogen (two atoms) and oxygen (one atom). They show better thermal stability, metabolic stability, aqueous solubility, and lower lipophilicity than the other isomeric oxadiazoles. They are important class of heterocycles present in many drug structures like Raltegravir, Furamizole Tidazosin, Nesapidil, Setileuton (MK-0633) and Zibotentan. The presence of this nucleus in therapeutics has made them an indispensable anchor for drug design and development. Several 1,3,4-oxadiazoles are prepared and reported as anticancer agents by numerous scientists worldwide. Objectives: The present review discusses the anticancer potentials together with the molecular targets of 1,3,4-oxadiazoles reported since 2010. The Structure-Activity Relationship (SAR) and molecular docking simulation on different targets have also been discussed herein. Some of the important cancer targets have also been explored. Methods: The most potent 1,3,4-oxadiazoles reported in the literature were highlighted in the manuscript. The anticancer activity was reported in terms of Growth Percent (GP), percent growth inhibition (%GI), GI50, IC50, and LC50 and TGI. Results: 1,3,4-Oxadiazoles are important heterocyclic scaffolds with broad spectrum biological activities. They may be either mono substituted or disubstituted, and they may act as an indispensable anchor for drug design and discovery due to their thermal stability together with low lipophilicity. They exhibited anticancer potentials and showed the inhibitions of various cancer targets. Conclusion: The discussion outlined herein will prove to be a helpful and vital tool for medicinal chemists investigating and working with 1,3,4-oxadiazoles and anticancer research programs.