Asymmetric Reactions of N-Phosphonyl/Phosphoryl Imines.

The asymmetric reactions of imines continued to attract the attention of the scientific community for decades. However, the stereoselective reactions of N-phosphonyl/phosphoryl imines remained less explored as compared to other N-substituted imines. The chiral auxiliary-based asymmetric-induction strategy with N-phosphonyl imines could effectively generate enantio- and diastereomeric amine, α,ß-diamine, and other products through various reactions. On the other hand, the asymmetric approach for the generation of chirality through the utilization of optically active ligands, along with metal catalysts, could be successfully implemented on N-phosphonyl/phosphoryl imines to access numerous synthetically challenging chiral amine scaffolds. The current review critically summarizes and reveals the literature precedence of more than a decade to highlight the major achievements existing to date that can display a clear picture of advancement as well drawbacks in this area.

Modulation of Covid-19 cytokine storm by tocilizumab.

Coronavirus disease 2019 (Covid-19) is the illness caused by severe acute respiratory syndrome coronavirus 2, first identified in Wuhan, China at the end of 2019. On March 11, 2020, the World Health Organization declared Covid-19 a global pandemic. The objective of this study is to determine the role of interleukin (IL) inhibitors in the treatment of Covid-19. By the majority of the reported clinical studies, the use of tocilizumab in Covid-19 infection appears promising in specific cases of the cytokine storm. Conflicting results prevent the recommendation of IL inhibitors against Covid-19 infection by many health organizations. However, many low-case fatality rate countries, with more advanced therapeutic approaches, uniformly include the use of tocilizumab in case of cytokine storms in addition to the standard treatment for severe cases which includes antivirals. Neglecting the other components is likely an explanation for the contradictory results found in the literature.

Green Synthetic Approach: An Efficient Eco-Friendly Tool for Synthesis of Biologically Active Oxadiazole Derivatives.

Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.

Tetrabutylammonium Bromide (TBAB) Catalyzed Synthesis of Bioactive Heterocycles.

During the last two decades, tetrabutylammonium bromide (TBAB) has gained significant attention as an efficient metal-free homogeneous phase-transfer catalyst. A catalytic amount of TBAB is sufficient to catalyze various alkylation, oxidation, reduction, and esterification processes. It is also employed as an efficient co-catalyst for numerous coupling reactions. It has also acted as an efficient zwitterionic solvent in many organic transformations under molten conditions. In this review, we have summarized the recent developments on TBAB-catalyzed protocols for the efficient synthesis of various biologically promising heterocyclic scaffolds.

Maximizing ISRIB Potential Requires Addressing Specificity, Long-Term Safety, and Disease-Specific Considerations.

BACKGROUND: Integrated Stress Response Inhibitor (ISRIB) works by inhibiting the integrated stress response, a cellular pathway involved in the regulation of protein synthesis during stress conditions. Conditions that have been studied or suggested as potential candidates for treatment with ISRIB include neurological and metabolic disorders, cognitive impairment, viral infections, and cancer. OBJECTIVE: The study aimed to discuss the challenges related to specificity, long-term safety, and disease-specific considerations crucial for realizing the full potential of ISRIB. METHOD: A narrative review of the literature has been conducted to delve into ISRIB's chemistry, mechanisms of action, disease-specific considerations, and long-term safety implications. RESULTS: While ISRIB has shown promising results in preclinical studies, more research is needed to determine its safety and effectiveness in human patients. Clinical trials are required to validate its therapeutic potential for various conditions. Despite having been proposed a decade ago, news of its clinical trials has been circulated only recently, without any published information yet and with rumors that its efficacy vs. safety profile may be compromised by side effects. CONCLUSION: While ISRIB offers exciting prospects for a range of biomedical applications, addressing challenges related to specificity, disease-specific considerations, and importantly long-term safety, is crucial for realizing its full potential.

Heterocyclic Phytochemicals as Anticancer Agents.

Cancer continues to be a major global health challenge, driving the need for the discovery of novel therapeutic agents. Among these, heterocyclic phytochemicals have gained significant attention for their potential as anticancer agents. This review offers a detailed analysis of various classes of heterocyclic compounds with proven anticancer properties, shedding light on their mechanisms of action. The study draws from a diverse array of natural product sources, detailing the chemical structures and bioactivities of these compounds. Key heterocyclic classes such as alkaloids, flavonoids, coumarins, and terpenoids are emphasized due to their potent anticancer effects. Heterocyclic phytochemicals exhibit diverse anticancer mechanisms, including the modulation of cellular pathways like apoptosis, angiogenesis, and cell cycle progression. The combination of heterocyclic phytochemicals with conventional cancer therapies has shown promising synergistic effects, enhanced treatment efficacy and reducing side effects. The review systematically evaluates both preclinical and clinical studies, revealing the efficacy, safety profiles, and pharmacokinetics of selected heterocyclic compounds. The promising outcomes highlighted in this review underscore the critical need for ongoing research to fully realize the therapeutic potential of heterocyclic phytochemicals in cancer treatment.

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

Reviewing the Synthesis and Clinical Application of FDA-Approved Anticancer Medications.

Cancer is a disease that affects people of all ages, socioeconomic backgrounds, genders, and demographics. It places a significant burden not just on those who are diagnosed but also on their families and communities. Targeted therapeutic medications have surpassed more conventional forms of chemotherapy in terms of both their effectiveness and safety, which leads to their rapid ascent to the forefront of cancer treatment. A growing number of small molecules have been created for the treatment of cancer, and several of these drugs have been approved to be sold in the market by the Food and Drug Administration of the United States. Small molecule targeted anticancer therapies have made significant progress in recent years, yet they continue to struggle with a number of obstacles, including a low response rate and drug resistance. We have carried out an exhaustive study on approved small-molecule targeted anticancer medications, as well as important drug candidates. This review describes the significance of approved anticancer drugs from 2021 to 2024, clinically active anticancer drugs, and the methods used for their synthesis.

Microwave-Induced Synthesis of Bioactive Nitrogen Heterocycles.

There are many different applications of heterocyclic molecules in the pharmaceutical and materials science fields, which make them an important family of compounds. Among these heterocyclic compounds, nitrogen-containing heterocyclic (N-heterocyclic) compounds have attracted a lot of interest among researchers due to their various applications across a wide variety of fields. Many studies have been performed over the past few years to study the synthesis of N-heterocycles under different reaction conditions, such as solvent-free, catalytic, reactants immobilized on a solid support, one-pot synthesis, and microwave irradiation. It has been demonstrated by our research group that microwaves can be utilized for rapid and efficient synthesis of biologically active compounds. In this review, we provide an overview of the microwave-assisted non-catalytic and catalytic preparation of nitrogen-containing heterocycles, mostly polycyclic N-heterocycles, five-membered N-heterocycles, six-membered N-heterocycles, and fused N-heterocycles. Mostly in this article, we explore the microwave-assisted preparation of biologically important compounds, such as pyrimidines, thiazoles, imines, tetrazoles, steroidal derivatives, quinolines, indolizine, triazoles, beta-lactams, pyrroles and quinoxalines.

Solar Light-Induced Synthesis of Biologically Active Compounds.

Over the past few years, photocatalytic methods have shown great promise as low-cost, environmentally friendly, and sustainable technologies. During the development of photochemistry, a variety of sources of light were used, including sunlight, compact fluorescent lamps, lasers, and even light-emitting diodes. As a part of preparing diverse organic compounds, the photochemical approach was used, for instance, to form rings, arylated compounds, cycloaddition, functionalized compounds, dehalogenated compounds, oxidized compounds, reduced compounds, isomers, and sensitized compounds. Solar energy is a renewable resource that can be harvested from the sun and this light energy can be changed into chemical energy with the help of photocatalysts. During this green approach, electron-hole pairs are generated in photocatalysts in order to begin reactions by using solar light. It has been highlighted in this article that there have been impressive developments in the use of light, mainly the solar light, to promote important organic reactions, which would otherwise be unattainable under thermal conditions.

Chemistry and Therapeutic Aspect of Triazole: Insight into the Structure-activity Relationship.

The triazole ring is a highly significant heterocycle that occurs naturally in many commodities and is a common feature in pharmaceuticals. Recently, heterocyclic compounds and their derivatives have been getting a lot of attention in medicinal chemistry because they have a lot of pharmacological and biological potential. For example, a lot of drugs have nitrogen-containing heterocyclic moieties. The triazole ring is often used as a bio-isostere of the oxadiazole nucleus. The oxygen atom in the oxadiazole nucleus is replaced by nitrogen in the triazole analogue. This article explores the pharmacological properties of the triazole moiety, including but not limited to antibacterial, analgesic, anticonvulsant, anthelmintic, anti-inflammatory, antitubercular, antimalarial, antioxidant, antiviral, and other properties. Additionally, we discuss the diverse multi- target pharmacological activities exhibited by triazole-based compounds. Based on a literature review, it is evident that triazole-based chemicals hold significant potential for various applications.

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities.

N-heterocyclic scaffolds represent a privileged architecture in the process of drug design and development. It has widespread occurrence in synthetic and natural products, either those that are established or progressing as potent drug candidates. Additionally, numerous novel N-heterocyclic analogues with remarkable physiological significance and extended pharmaceutical applications are escalating progressively. Hence, the classical synthetic protocols need to be improvised according to modern requirements for efficient and eco-friendly approaches. Numerous methodologies and technologies emerged to address the green and sustainable production of various pharmaceutically and medicinally important N-heterocyclic compounds in last few years. In this context, the current review unveils greener alternatives for direct access to categorically differentiated N-heterocyclic derivatives and its application in the establishment of biologically active potent molecules for drug design. The green and sustainable methods accentuated in this review includes microwave-assisted reactions, solvent-free approaches, heterogeneous catalysis, ultrasound reactions, and biocatalysis.

Biological Effects and Mechanisms of Taurine in Various Therapeutics.

More than two hundred years ago, taurine was first isolated from materials derived from animals. It is abundantly found in a wide range of mammalian and non-mammalian tissues and diverse environments. Taurine was discovered to be a by-product of the metabolism of sulfur only a little over a century and a half ago. Recently, there has been a renewed academic interest in researching and exploring various uses of the amino acid taurine, and recent research has indicated that it may be useful in the treatment of a variety of disorders, including seizures, high blood pressure, cardiac infarction, neurodegeneration, and diabetes. Taurine is currently authorised for the therapy of congestive heart failure in Japan, and it has shown promising results in the management of several other illnesses as well. Moreover, it was found to be effective in some clinical trials, and hence it was patented for the same. This review compiles the research data that supports the prospective usage of taurine as an antibacterial, antioxidant, anti-inflammatory, diabetic, retinal protective, and membrane stabilizing agent, amongst other applications.

Mechanistic Role of Tempol: Synthesis, Catalysed Reactions and Therapeutic Potential.

Tempol (TP) was introduced in 1960 by Lebedev and Kazarnovskii and is an excellent catalyst extensively used in the synthesis and oxidation of various reagents. 4-Hydroxy-2,2,6,6- tetramethylpiperidin-1-oxyl (TP) has also been explored against various disorders like inflammation, superoxide anion-influenced molecular linked behavioural modifications, radical capturing, cardioprotective, protective ocular damage, against skin burns, fibrocystic diseases, breast cancer prevention, respiratory infections, alopecia, and cerebral malaria, etc. This review article comprises five major aspects of TP namely (a) Approx. 25 different Synthesis schemes of TP (b) major reactions catalysed by TP (c) Therapeutic potential of TP. It also provides scientific information that supports the use of TP which may be proven as a "MIRACLE" drug for the treatment of numerous disorders namely in reducing the reactive oxygen species, superoxide mutases, vision disorders, cancer as well as in covid. It also possesses a significant role in minimising side effects in combination therapy. This review will be beneficial to researchers, healthcare, and academic professionals for further research.

Carbapenem Antibiotics: Recent Update on Synthesis and Pharmacological Activities.

Right from the breakthrough of carbapenems since 1976, many schemes on synthesis, structure-activity relationship (SAR), and biological activities have been carried out, and several carbapenems have been developed, including parentally active carbapenems like imipenem, doripenem, biapenem, meropenem, ertapenem, panipenem, razupenem, tomopenem, and cilastatin, whereas orally active carbapenems like GV-118819, GV-104326, CS-834, L-084, DZ-2640, CL 191, 121, L-646, 591, S-4661, ER-35768, MK-826. Prodrugs of carbapenem with increased bioavailability include temopenem, tebipenem, sanfetrinem, LK-157, and CP 5484. Merck, Glaxo Welcome Research Group, Johnson & Johnson, Sankyo Group and Dai-ichi Group, and Wyeth-Ayerst Group were among the businesses that produced carbapenems. In this review Witting reaction, Mitsunobu reaction, Dieckmann reaction, palladium-catalyzed hydrogenolysis, E. coli-based cloned synthesis, as well as biosynthetic enzymes such as carbapenem synthetase (carA), carboxymethylproline synthase (carB), carbapenem synthase (carC) are included. Carbapenems are biologically mainly active in the infections like urinary tract infections, bloodstream infections, tuberculosis, intra-abdominal infections, and pathogens like anaerobes, gram-positive and gram-negative bacteria.

Microwave Induced Green Synthesis: Sustainable Technology for Efficient Development of Bioactive Pyrimidine Scaffolds.

Microwave radiation is used as a heating source during the synthesis of heterocyclic compounds. The heating mechanisms involved in microwave-induced synthesis include dipolar polarization and ionic conduction. This heating technology follows the green protocol as it involves the use of recyclable organic solvents during synthesis. The microwave heating approach offers a faster rate of reaction, easier work-up procedure, and higher product yield with purity and also reduces environmental pollution. So, microwave heating is applied as a sustainable technology for the efficient production of pyrimidine compounds as one of the heterocyclic moieties. Pyrimidine is a six-membered nitrogenous heterocyclic compound that plays a significant role due to several therapeutic applications. This moiety acts as an essential building block for generating drug candidates with diverse biological activities, including anti-cancer (capecitabine), anti-thyroid (propylthiouracil), antihistaminic (pemirolast), antimalarial (pyrimethamine), antidiabetic (alloxan), antihypertensive (minoxidil), anti-inflammatory (octotiamine), antifungal (cyprodinil), antibacterial (sulfamethazine), etc. This review is focused on the synthesis of pyrimidine analogs under microwave irradiation technique and the study of their therapeutic potentials.

A microwave-assisted bismuth nitrate-catalyzed unique route toward 1,4-dihydropyridines.

The classical Hantzsch reaction is one of the simplest and most economical methods for the synthesis of biologically important and pharmacologically useful 1,4-dihydropyridine derivatives. Bismuth nitrate pentahydrate under microwave irradiation is proven to act as a very efficient catalyst for a one-pot, three-component synthesis of 1,4-dihydropyridines in excellent yields from diverse amines/ammonium acetate, aldehydes and 1,3-dicarbonyl compounds within 1-3 min under solvent-free conditions. The present environmentally benign procedure for the synthesis of 1,4-dihydropyridines is suitable for library synthesis and it will find application in the synthesis of potent biologically active molecules. The excellent yield and extreme rapidity of the method is due to a concurrent effect of the catalyst and microwave irradiation.

An expeditious iodine-catalyzed synthesis of 3-pyrrole-substituted 2-azetidinones.

2-Azetidinones and pyrroles are two highly important classes of molecules in organic and medicinal chemistry. A green and practical method for the synthesis of 3-pyrrole-substituted 2-azetidinones using catalytic amounts of molecular iodine under microwave irradiation has been developed. Following this method, a series of 3-pyrrole- substituted 2-azetidinones have been synthesized with a variety of substituents at N-1 and at C-4. The procedure is equally effective for mono- as well as polyaromatic groups at the N-1 position of the 2-azetidinone ring. The C-4 substituent has no influence either on the yield or the rate of the reaction. Optically pure 3-pyrrole-substituted 2-azetidinones have also been synthesized following this methodology. No deprotection/rearrangement has been identified in this process, even with highly acid sensitive group-containing substrates. A plausible mechanistic pathway has also been suggested based on the evidence obtained from ¹H-NMR spectroscopy. The extreme rapidity with excellent reaction yields is believed to be the result of a synergistic effect of the Lewis acid catalyst (molecular iodine) and microwave irradiation.

Reactive Oxygen Species (ROS): Key Components in Cancer Therapies.

Reactive Oxygen Species (ROS) refers to the highly reactive substances which contain oxygen radicals. Hypochlorous acid, peroxides, superoxide, singlet oxygen, alpha-oxygen, and hydroxyl radicals are the major examples of ROS. Generally, the reduction of oxygen (O2) in molecular form produces superoxide (•O2 -) anion. ROS are produced during a variety of biochemical reactions within the cell organelles, such as endoplasmic reticulum, mitochondria, and peroxisome. Naturally, ROS are also formed as a byproduct of the normal metabolism of oxygen. The production of ROS can be induced by various factors such as heavy metals, tobacco, smoke, drugs, xenobiotics, pollutants, and radiation. From various experimental studies, it is reported that ROS acts as either a tumor-suppressing or a tumor-promoting agent. The elevated level of ROS can arrest the growth of tumors through the persistent increase in cell cycle inhibition. The increased level of ROS can induce apoptosis by both intrinsic and extrinsic pathways. ROS is considered to be a tumor-suppressing agent as the production of ROS is due to the use of most of the chemotherapeutic agents in order to activate cell death. The cytotoxic effect of ROS provides impetus towards apoptosis, but in higher levels, ROS can cause initiation of malignancy that leads to uncontrolled cell death in cancer cells. In contrast, some species of ROS can influence various activities at the cellular level, including cell proliferation. This review highlights the genesis of ROS within cells by various routes and their role in cancer therapies.

Use of Ultraviolet Blood Irradiation Against Viral Infections.

Ultraviolet blood irradiation (UBI) was used with success in the 1930s and 1940s for a variety of diseases. Despite the success, the lack of understanding of the detailed mechanisms of actions, and the achievements of antibiotics, phased off the use of UBI from the 1950s. The emergence of novel viral infections, from HIV/AIDS to Ebola, from SARS and MERS, and SARS-CoV-2, bring back the attention to this therapeutical opportunity. UBI has a complex virucidal activity, mostly acting on the immune system response. It has effects on lymphocytes (T-cells and B-cells), macrophages, monocytes, dendritic cells, low-density lipoprotein (LDL), and lipids. The Knott technique was applied for bacterial infections such as tuberculosis to viral infections such as hepatitis or influenza. The more complex extracorporeal photopheresis (ECP) is also being applied to hematological cancers such as T-cell lymphomas. Further studies of UBI may help to create a useful device that may find applications for novel viruses that are resistant to known antivirals or vaccines, or also bacteria that are resistant to known antibiotics.