Structural activity relationship of metallo-aminoquines as a next generation antimalarials

Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria, one of the most devastating, furious and common infectious disease throughout the world. According to the latest World malaria report, there were 229 million cases of malaria in 2019 majorly consisting of children under 5 years of age. Some of known analogues viz. quinine, quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades have witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. For the past few decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1), Ruthenoquine (RQ or 2) and other related potent metal-analogues. It observed that some metal containing analogues (Fe-, Rh-, Ru-, Re-, Au-, Zn-, Cr-, Pd-, Sn-, Cd-, Ir-, Co-, Cu-, and Mn-aminoquines) were more potent; however, some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches, which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus, this review aims to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amoniquines.

Emerging Role of Flavonoids as the Treatment of Depression

Depression is one of the most frequently observed psychological disorders, affecting thoughts, feelings, behavior and a sense of well-being in person. As per the WHO, it is projected to be the primitive cause of various other diseases by 2030. Clinically, depression is treated by various types of synthetic medicines that have several limitations such as side-effects, slow-onset action, poor remission and response rates due to complicated pathophysiology involved with depression. Further, clinically, patients cannot be given the treatment unless it affects adversely the job or family. In addition, synthetic drugs are usually single targeted drugs. Unlike synthetic medicaments, there are many plants that have flavonoids and producing action on multiple molecular targets and exhibit anti-depressant action by affecting multiple neuronal transmissions or pathways such as noradrenergic, serotonergic, GABAnergic and dopaminergic; inhibition of monoamine oxidase and tropomyosin receptor kinase B; simultaneous increase in nerve growth and brain-derived neurotrophic factors. Such herbal drugs with flavonoids are likely to be useful in patients with sub-clinical depression. This review is an attempt to analyze pre-clinical studies, structural activity relationship and characteristics of reported isolated flavonoids, which may be considered for clinical trials for the development of therapeutically useful antidepressant.

Design, Synthesis, Molecular Docking and Biological Evaluation of Novel 2-[(2-{[5-(Pyridin-4-yl)-1, 3, 4-Oxadiazol-2-yl]Sulfanyl}Ethyl)Sulfanyl]-1,3-Benzoxazole

In the present communication, a simple and facile method was adopted to synthesize a series of novel 2-[(2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfanyl}ethyl)sulfanyl]-1,3-benzoxazole by fusing 5-(pyridin-4-yl)-1,3,4-oxadiazole-2-thiol with substituted 2-[(2-bromoethyl)sulfanyl]-1,3-benzoxazole and 2-[(2-chloroethyl)sulfanyl]-1,3-benzoxazole to obtain heterocyclic ring systems of 1,3,4 oxadiazole linked benzoxazole moiety. The synthesized compounds were characterized by the aid of LCMS, IR, 1H NMR, 13CNMR, and C, H, N analysis technique. All the newly synthesized compounds were assessed for antimicrobial, antioxidant and antitubercular activities against standard strains. Microbiological results showed that the compounds showcased a wide range of activities and further the results of antimicrobial, antioxidant and molecular docking studies revealed that the compounds 6c, 6d and 6e are more potent and displays excellent docking scores with various amino acids interaction like alkyl-alkyl, pi-alkyl and hydrogen bonding of antitubercular receptor H37R with benzoxazole moieties and displayed encouraging antitubercular results to 6c, 6d and 6e molecules. The structural activity relationship studies illuminated the obtained results.

Structural Activity Relationship-based Medicinal perspectives of Pyrimidine derivatives as Anti-Alzheimer’s Agent: A Comprehensive Review

: Pyrimidine is an aromatic and heterocyclic organic compound containing a 6-membered ring consisting of four carbon and two nitrogen atoms on an alternative position. Pyrimidine scaffolds described its existence between the medicinal chemist’s cause of its synthesizing practicability and nonpoisonous nature. However, the reason behind the neurological disorder is still an open challenge in scientific research and development organizations. Despite high throughput research in the field of anti-Alzheimer’s drugs, the efficacy void is quite common before the researchers. Researchers have constantly investigated all the probabilities to restraint the unwanted adverse effects of the anti-Alzheimer’s agents or focusing on a more considerable perspective to decline or rehabilitate neurological disorder. The drug development has revealed aspiration to medicinal chemists and researchers to felicitate research by look over through a considerable literature survey. Therefore, the SAR study-based approach has been emphasized that pharmacological advancements of Pyrimidine moiety in the new era as therapeutics anti-Alzheimer’s agents.

Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

Novel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.

Recent Trends in the Development of Benzimidazole Hybrid Derivatives and Their Antimalarial Activities

A parasite of the Plasmodium species initiates malaria. The parasite is transmitted to communities through the bite of an infected mosquito. Malarial resistance towards the commonly used antimalarial agents is a genuine human health problem. Benzimidazole derivatives exhibit a wide range of antimalarial activities against Plasmodium falciparum (P. falciparum) strain. The present review has summarized the antimalarial activity of benzimidazole hybrid derivatives and described its structural activity relationship (SAR) and quantitative structural-activity relationship (QSAR) model. A total of 14 papers were systematically reviewed. The literature survey has revealed that novel benzimidazole hybrid derivatives diminished the P. falciparum activity in the liver and gametocyte stages and inhibited heme synthesis and β-hematin formation. The QSAR models explain imminent antimalarial agent's growth through multiple linear regression (MLR) and artificial neural networks (ANN).

Synthesis and Biological Screening of New Thiadiazolopyrimidine-based Polycyclic Compounds

New tri- and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were prepared and their antimicrobial activity were estimated. The achieved results evidenced that pyrano-thiadiazolopyrimidine compounds 8a-b and 9a-b have substantial efficiencies toward the two strains of Gram-positive bacteria (S. aureus and B. cereus). While tetracyclic derivatives pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a-b and 17a-b displayed prominent efficiencies toward the two strains of Gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a-b and 9a-b presented good efficacy toward C. albicans. The activity of antiquorum-sensing (anti-QS) inhibition of the new synthesized thiadiazolopyrimidine-based compounds was tested toward C. violaceum, where derivatives 16a-b, 17a-b, 8b and 9a displayed satisfactory activity. Cytotoxic activity of the same derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2 and HepG2) and standard normal fibroblast cell (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b, 17a and 17b recorded potent cytotoxic efficacy against MCF-7 cells with IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) for the inspected thiadiazolopyrimidine derivatives provided an awareness concerning the chemical structure connected to anticancer efficiency. In silico docking studies were implemented toward silence hormone signaling in breast (PDB Code-5NQR). The results are consistent and supportive to the cytotoxic activity.

Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review

: As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact on chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is to discover novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

Chemoinformatic analysis of alkaloids isolated from Peganum genus

Peganum genus is rich with its high phytochemical and botanical variability. Peganum species have been used as sedative, antitumor, analgesics, antidepressant, and other medicinal purposes. The aim of this research is to study the molecular diversity of Peganum genus to shed more lights on the structure-activity relationship of the alkaloids isolated from Peganum genus. All Peganum alkaloids were grouped according to their structure properties. A chemoinformatic approach (Swiss Model) was used to determine the molecular targets of these alkaloids. To visualize the results, R programming language was used to generate hierarchical clustering heatmaps. The results of this study helps researcher to better understanding of the structural-activity relationship of Peganum alkaloids.