Design, Synthesis, and Characterization of Novel Series of Pharmacologically-important Sperm-shaped Amphiphilic Heterocyclic Compounds derived from Natural Palmitic Acid

Natural palmitic acid is a pivotal saturated fatty acid used in many biochemical processes occurring in humans and diverse living creatures, as it is the most common natural long-chain carboxylic acid whose unrivaled amphiphilic sperm-like skeleton with the inert single 15-C aliphatic chain (tail or carrier) and the very active one carboxyl group (head) represent a rich reactive entity and carrier for several organic/medicinal chemistry and pharmaceutics applications with respect to drug design and formulation. Derivatives of 1,3,4-oxadiazoles along with their 1,3,4-thiadiazoles and 1,2,4-triazoles analogs exhibit a broad spectrum of substantial pharmacological activities. Agreeing with the well-known hybridization principles and incorporation norms in hybrid chemistry, if a substituted nitrogenous heterocyclic aromatic nucleus of the three aforementioned kinds is straightway attached to the simple straight palmitic acid backbone at the position of the carboxyl group, the produced molecules are supposed to be very bioactive. This research work reports for the first once the efficient design/synthesis and characterization/elucidation of four one-tailed nitrogen-containing heterocyclic derivatives of palmitic acid constructure, which introduce a novel biologically-important pharmacophore having biocompatible amphiphilic sperm-shaped heteroaromatic structure.

A medicinal chemist’s perspective towards structure activity relationship of heterocycle based anti-cancer agents

Aim: To describe structure activity relationship of heterocyclic derivatives with multi-targeted anticancer activity. Objectives: With the following goals in mind, this review tries to describe significant recent advances in the medicinal chemistry of heterocycle-based compounds: (1) To shed light on recent literature focused on heterocyclic derivatives' anticancer potential; (2) To discuss recent advances in the medicinal chemistry of heterocyclic derivatives, as well as their biological implications for cancer eradication; (3) To summarise the comprehensive correlation of structure activity relationship (SAR) with pharmacological outcomes in cancer therapy. Background: Cancer remains one of the major serious health issues devastating the world today. Cancer is a complex disease in which improperly altered cells proliferate at an uncontrolled, rapid, and severe rate. Variables such as poor dietary habits, high stress, age, and smoking, can all contribute to the development of cancer. Cancer can affect almost any organ or tissue, although the brain, breast, liver, and colon are the most frequently affected organs. From several years, surgical operations and irradiation are in use along with chemotherapy as a primary treatment of cancer but still effective treatment of cancer remains a huge challenge. Chemotherapy is now one of the most effective strategies to eradicate cancer, although it has been shown to have a number of cytotoxic and unfavourable effects on normal cells. Despite all of these cancer treatments, there are several other targets for anticancer drugs. Cancer can be effectively eradicated by focusing on these targets, which include both cell-specific and receptor-specific targets such as tyrosine kinase receptors (TKIs). Heterocyclic scaffolds also have a variety of applications in drug development and are a common moiety in the pharmaceutical, agrochemical, and textile industries. Methods: The association between structural activity relationship data of many powerful compounds and their anticancer potential in vitro and in vivo has been studied. SAR of powerful heterocyclic compounds can also be generated using molecular docking simulations, as reported vastly in literature. Conclusions: Heterocycles have a wide range of applications, from natural compounds to synthesised derivatives with powerful anticancer properties. To avoid cytotoxicity or unfavourable effects on normal mammalian cells due to a lack of selectivity towards the target site, as well as to reduce the occurrence of drug resistance, safer anticancer lead compounds with higher potency and lower cytotoxicity are needed. This review emphasizes on design and development of heterocyclic lead compounds with promising anticancer potential.

Inhibitory Activities of Pyrazolo-Oxazine Heterocyclic Derivatives

Despite several reports and reviews addressing the biological significance of pyrazoles and oxazines, no comprehensive work on the pyrazolo oxazine fused ring system has been published so far.We report all biological evaluations on pyrazolo-oxazine derivatives in this mini-review to provide an avenue for medicinal and pharmacological researchers to conduct further in-depth exploration.

Green Multi-Component Synthesis of Fused heterocyclic derivatives: An atom economic ecofriendly approach for complex molecules

Background: The construction of fused heterocyclic compounds is always fascinating on the strength of their applications as novel pharmaceuticals. Multi-component reactions (MCRs) are atom economical, beneficial, straightforward and ecofriendly approach for synthesis of complex heterocycles in a single step with higher selectivity. Methods: The review mainly focused on the synthesis of fused heterocycles such as pyrimidine - chromene, Pyrrolo - pyrazine, Pyrazolo - pyrimidine, pyran - imidazole and pyrazole- imidazole - pyrimidine, pyran - pyridmidone, pyrrolo - chromene, pyridine-pyrimidinone, fused indole derivatives, furano - pyran along with some simple MCRs discussed, which published in in the period of 2019 and 2020. A table of summary about 50 heterocycles with product, catalysts and cited literature for are given at end. Conclusions: From this review we understand that MCRs can deliver an effortless access to molecular targets of our interest with wide choice of reactants and their combinations. Thus, the creativity and choice of reactants are pushing the development in MCRs towards more atom economical and eco-friendly approach Objective: Understanding recent trends in the development of MCRs is a requisite for anyone, who wish to synthesise simple and fused heterocycles. By keeping this as primary objective, the present review provides an overview of latest developments in fused heterocyclic synthesis via green multicomponent reactions in the period of 2019 and 2020.

Computational Study of the Therapeutic Potential of Novel Heterocyclic Derivatives against SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV-2), including the recently reported severe variant B.1.617.2, has been reported to attack the respiratory tract with symptoms that may ultimately lead to death. While studies have been conducted to evaluate therapeutic interventions against the virus, this study evaluated the inhibitory potential of virtually screened novel derivatives and structurally similar compounds towards SARS-CoV-2 via a computational approach. A molecular docking simulation of the inhibitory potentials of the compounds against the SARS-CoV-2 drug targets—main protease (Mpro), spike protein (Spro), and RNA-dependent RNA polymerase (RdRp)—were evaluated and achieved utilizing AutoDock Vina in PyRx workspace. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of these compounds were assessed using SwissADME and ADMETLab servers. All the compounds displayed high binding affinities for the SARS-CoV-2 drug targets. However, the C13 exhibited the highest binding affinity for the drug targets, Spro and RdRp, while C15 exhibited the highest binding affinity for Mpro. The compounds interacted with the LEU A:271, LEU A:287, ASP A:289, and LEU A:272 of Mpro and the HIS A:540, PRO A:415, PHE A:486, and LEU A:370 of the Spro receptor binding motif and some active site amino acids of RdRp. The compounds also possess a favourable ADMET profile and showed no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. These novel compounds could offer therapeutic benefits against SARS-CoV-2, and wet laboratory experiments are necessary to further validate the results of this computational study.

Synthesis of bis-Heterocyclic Derivatives of Thiohydantoin

The possibility of structural modification of thiohydantoin derivatives via amidoalkylation under the action of a range of cyclic hemiamidals is demonstrated. The suggested approach provides, in particular, unsymmetrical nitrogen-containing bis-heterocyclic systems with pharmacologically relevant groups that are difficult to obtain by other methods.