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.

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.

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.

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.

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.

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.

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.

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.

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.

Recent Advances in the Development of Broad-Spectrum Antiprotozoal Agents.

Infections caused by Trypanosoma brucei, Trypanosoma cruzi, Leishmania spp., Entamoeba histolytica, Giardia lamblia, Plasmodium spp., and Trichomonas vaginalis, are part of a large list of human parasitic diseases. Together, they cause more than 500 million infections per year. These protozoa parasites affect both low- and high-income countries and their pharmacological treatments are limited. Therefore, new and more effective drugs in preclinical development could improve overall therapy for parasitic infections even when their mechanisms of action are unknown. In this review, a number of heterocyclic compounds (diamidine, guanidine, quinoline, benzimidazole, thiazole, diazanaphthalene, and their derivatives) reported as antiprotozoal agents are discussed as options for developing new pharmacological treatments for parasitic diseases.

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.

Microwave-Induced Ugi-Four Component Reactions: Synthesis of New Hetero- Steroid-Amino Acid Conjugates.

BACKGROUND: Aza-steroids are an important class of compounds because of their numerous biological activities. The hetero steroids have different hydrogen bonding ability and hydrophobicity in comparison to steroids. MATERIALS AND METHODS: Microwave-induced synthesis of a novel type of hybrid hetero-steroid amine conjugates, following Ugi-four component reactions of steroidal amines with alanine and valine methyl esters as amino acid residues is described. Specifically, hetero-steroid-amino acid conjugate based on D-ring fused hetero steroidal amine, hetero-steroid-amino acid conjugate based on A-ring hetero steroidal amine, and hetero-steroidamino acid conjugate based on B-ring hetero steroidal amine are synthesized. RESULTS AND DISCUSSION: The yield of the products under microwave-induced process was considerably higher than that obtained by the conventional method. In contrast to the conventional method for the synthesis of these molecules, microwave-induced method has several advantages. CONCLUSION: These include rapid reaction, a superior yield of the product, minimum side reaction, and economical microwave-induced process.

Polyaromatic Hydrocarbons (PAHs): Structures, Synthesis and their Biological Profile.

Polycyclic aromatic hydrocarbons (PAHs) are aromatic compounds with two or more fused benzene rings in their structural configurations. PAHs do not contain heteroatoms and substituents on the ring system. PAHs containing up to four rings are called light PAHs while those that contain more than four rings are considered as heavy PAHs. Heavy PAHs are more stable and more toxic than the light PAHs. Generally, the increase in the size and angularity of a PAH molecule results in an increase in hydrophobicity and electrochemical stability. Ring linkage patterns in PAHs may occur in such a way that the tertiary carbon atoms are centers of two or three interlinked rings. The examples of PAHs are naphthalene, anthracene, phenanthrene, acenaphthylene, acenaphthene, fluorene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, etc. PAHs can be produced either naturally or anthropogenically and have toxic properties. Due to the health risk posed by their exposure, there is a need to control the release of PAHs through air quality management. Refinery industries are required to monitor and regulate their discharges. There is an urgent need for the considerable efforts to be applied in the field of research to degrade and monitor potentially hazardous substances to control, predict and avoid negative effects of PAHs pollution.

An Overview on Steroids and Microwave Energy in Multi-Component Reactions towards the Synthesis of Novel Hybrid Molecules.

In recent years, hybrid systems are gaining considerable attention owing to their various biological applications in drug development. Generally, hybrid molecules are constructed from different molecular entities to generate a new functional molecule with improved biological activities. There already exist a large number of naturally occurring hybrid molecules based on both non-steroid and steroid frameworks synthesized by nature through mixed biosynthetic pathways such as, a) integration of the different biosynthetic pathways or b) Carbon- Carbon bond formation between different components derived through different biosynthetic pathways. Multicomponent reactions are a great way to generate efficient libraries of hybrid compounds with high diversity. Throughout the scientific history, the most common factors developing technologies are less energy consumption and avoiding the use of hazardous reagents. In this case, microwave energy plays a vital role in chemical transformations since it involves two very essential criteria of synthesis, minimizing energy consumption required for heating and time required for the reaction. This review summarizes the use of microwave energy in the synthesis of steroidal and non-steroidal hybrid molecules and the use of multicomponent reactions.

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specifically address the cytokines' storm characteristic of the Acute Respiratory Distress Syndrome (ARDS) that occur in the later cycle of the Covid19 infectious disease.

A Versatile Method for the Protection of Carbonyl Compounds by Camphor Sulfonic Acid.

BACKGROUND: Carbonyl groups are important functional groups and they play a key role in organic chemistry. This group needs to be protected in multistep synthesis against various reagents for a counter-reaction. The effort towards developing an efficient methodology for the protection of car-bonyl functional group is always a demanding reaction. The protection of carbonyl compounds for in-hibiting their chemical reactivity is an important operation in chemistry. In this paper, camphor sulfonic acid-catalysed protection of various carbonyl compounds is developed. This method is simple, envi-ronmentally friendly and yields products in high yields. METHOD: Commercially available camphor sulfonic acid is used as organo-catalyst for the protection of carbonyl functionality. This catalyst is also employed for the protection of carbonyl functionality as thi-oacetal/mixed ketal in excellent yield. The newly synthesize compounds are characterized using 1HNMR, 13C NMR and IR spectroscopy. RESULT: A diverse carbonyl functional group is protected in excellent yield under mild reaction condi-tions. CONCLUSION: We have developed an efficient organocatalysed protection method of carbonyl function-ality applicable to wide range of substrates.