Mini Reviews in Medicinal Chemistry - Volume 21, Issue 9, 2021

Phytocompounds are long known for their therapeutic uses due to their competence as antimicrobial agents. The antimicrobial activity of these bioactive compounds manifests their ability as an antibiofilm agent and is thereby proved to be competent to treat the widespread biofilm-associated chronic infections. The rapid development of antibiotic resistance in bacteria has made the treatment of these infections almost impossible by conventional antibiotic therapy, which forced a switch-over to the use of phytocompounds. The present overview deals with the classification of a huge array of phytocompounds according to their chemical nature, detection of their target pathogen, and elucidation of their mode of action.

Thiazolo- and thiadiazolo-[3,2-a][1,3]diazepines and their patented derivatives, tested with diverse CNS pharmacological activities, constitute an important class of compounds for new drug development. Therefore, research efforts were continued to design, synthesize, and evaluate compounds for their ultra-short, short-acting hypnotic, anticonvulsant, and neuromuscular blocking activities. The present review provides a summary of the work accomplished by these heterocycles and their biological evaluation.

Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.

Azo molecules possess the characteristic azo bond (-N=N-) and are considered fascinating motifs in organic chemistry. Since the last century, these brightly colored compounds have been widely employed as dyes across several industries in applications for printing, food, paper, cosmetics, lasers, electronics, optics, material sciences, etc. The discovery of Prontosil, an antibacterial drug, propelled azo compounds into the limelight in the field of medicinal chemistry. Subsequent discoveries including Phenazopyridine, Basalazide, and Sulfasalazine enabled azo compounds to occupy a significant role in the drug market. Furthermore, azo compounds have been employed as antibacterial, antimalarial, antifungal, antioxidant, as well as antiviral agents. The metabolic degradation of many azo dyes can induce liver problems if ingested, posing a safety concern and limiting their application as azo dyes in medicinal chemistry. However, azo dyes remain particularly significant for applications in cancer chemotherapy. Recently, a paradigm shift has been observed in the use of azo dyes: from medicinal chemistry to biomedical sciences. The latter benefits from azo dye application are related to imaging, drug delivery, photo-pharmacology and photo switching. Herein, we have compiled and discussed recent works on azo dye compounds obtained so far, focusing on their medicinal importance and future prospects.

Production of particles and their adaptation in the pharmacology became an object of interest, and they are the currently introduced therapies based on the use of micro and nanoparticles. The use of gold particles is not an exception. This review has focused on the application of gold micro and nanoparticles in pharmacology and biomedicine. The particles can be used for diagnosis respective theranostic of cancer, rheumatoid arthritis and as antimicrobial means. Besides these applications, specifications of gold, gold particles, and colloidal gold manufacturing and their comparison with the solid gold, are described as well. This review is based on a survey of actual scientific literature.

Isatin is an endogenous and a significant category of fused heterocyclic components and has widely been a part of several potential biologically useful synthetics. Since its discovery, tons of research work has been conducted with respect to the synthesis, chemical properties, and biological and industrial applications. It contains an indole nucleus having both lactam and keto moiety, which, while being a part of a molecular framework, exerted several biological effects, viz.; anti-microbial, anti-tubercular, anticonvulsant, anti-cancer, etc. Isatin derivatives are synthetically significant substrates, which can be utilized for the synthesis of huge diversified chemical entities of which few members emerged as drugs. The reason for this review is to provide extensive information pertaining to the chemistry and its significance in altering several pathological states of isatin and its derivatives. A Structure-Activity Relationship study thus developed through a gamut of scientific information indicates the importance of mostly electron-withdrawing groups, halogens, nitro, alkoxy, and, to a minor extent, groups with positive inductive effects, such as methyl at position 1, 5, 6 and 7 of isatin in alleviating several clinical conditions. It is also observed from the survey that the presence of two oxo groups at positions 2 and 3 sometimes becomes insignificant as a fusion with a heterocycle at these positions resulted in a biologically relevant compound.

Tumor cells frequently reprogram cellular metabolism from oxidative phosphorylation to glycolysis. Isocitrate dehydrogenase 2 (IDH2) has been intensively studied due to its involvement in the metabolic activity of cancer cells. Mutations in IDH2 promote neomorphic activity through the generation of oncometabolite 2-hydroxyglutarate (2-HG). The overproduced 2-HG can competitively inhibit α-KG-dependent dioxygenases to trigger cell differentiation disorders, a major cause of blood tumors. This review outlines recent progress in the identification of IDH2 inhibitors in blood cancer to provide a reference for ongoing and future clinical studies.

COVID-19 is a public health emergency of international concern. Although considerable knowledge has been acquired with time about the viral mechanism of infection and mode of replication, yet no specific drugs or vaccines have been discovered against SARS-CoV-2 to date. There are few small molecule antiviral drugs like Remdesivir and Favipiravir, which have shown promising results in different advanced stages of clinical trials. Chloroquinine, Hydroxychloroquine, and Lopinavir- Ritonavir combination, although initially were hypothesized to be effective against SARSCoV- 2, are now discontinued from the solidarity clinical trials. This review provides a brief description of their chemical syntheses along with their mode of action, and clinical trial results available on Google and in different peer-reviewed journals till 24th October 2020.

Background and Objective: Maternal separation as an epigenetic agent provokes a severe change in the brain, such as inflammation response, which is a key risk factor for the progression of autism spectrum disorders (ASD). This study evaluated the preventive effect of hypericin on maternal separation-induced cognitive deficits and hippocampal inflammation. Methods: Here, we reported that pups are subjected to maternal separations for 1 h per day from postnatal days (PND) 1-9 displayed apparent memory impairment in young rats (postnatal day 34) compared to controls group. Furthermore, maternal separation significantly increased inflammation factors in the hippocampus area. Anti-inflammation constituent shed light on treating ASD. Results: In this study, we found that treatment with hypericin (10 and 50 mg/kg) significantly suppresses expression of hippocampal interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the maternal separation rat model. Also, we found that hypericin prevented the decrease of hippocampal dopamine levels in the offspring of maternal separation rats. Conclusion: The data indicated that hypericin may play a neuroprotective role in hippocampal cell and ameliorates dysfunctions in memory and level of inflammation factor in this autism model. Thus, hypericin could be used as an intervention for treating ASD.