"Naringenin: A Promising Immunomodulator for Anti-Inflammatory, Neuroprotective, and Anti-Cancer Applications".

BACKGROUND: Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with inter-twined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments. OBJECTIVE: This review offers an encompassing exploration of naringenin's anti-inflamma-tory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations. METHODS: Data for this review were amassed through the scrutiny of various published studies via search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced. RESULTS: Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions. CONCLUSION: Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of in vivo data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.

Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies.

BACKGROUND: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors. AIMS: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. METHODS: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. RESULTS: The ADME profile of synthesized compounds was found to be satisfactory. CONCLUSION: The synthesized compounds can serve as lead for further drug designing.

In-Silico Design, Synthesis, and Pharmacological Evaluation of Oxadiazole-Based Selective Cyclo-oxygenase-2 Inhibitors.

A series of oxadiazole-based five-membered heterocyclic derivatives was designed and synthesized with the intent of exclusive cyclo-oxygenase-2 (COX-2) inhibition to acquire anti-inflammatory activity without the presence of gastric toxicity. Oxadiazole-based novel analogs were designed by using bioisosteric substitutions and were screened against the macromolecular target by using docking-based virtual screening to identify their potential inhibitors. These selective COX-2 inhibitors were further evaluated for their stability within the binding cavity of macromolecular complex by performing molecular dynamic simulation for 100 ns. Selected compounds were synthesized by using Naphthalene-2-yl-acetic acid as a starting material based on the fundamental structure of naphthalene. The naphthalene ring and methylene bridge of naphthalene-2-yl-acetic acid were retained in the rational molecular design by replacing the carboxyl group with biologically significant groups like 1,3,4-oxadiazoles, with the goal of obtaining a novel, superior, and relatively safe anti-inflammatory molecule with better efficacy and optimized pharmacokinetics. Anti-inflammatory as well as analgesic properties of the compounds were evaluated experimentally for their pharmacological efficiency.

Recent insights into antibacterial potential of benzothiazole derivatives.

Antimicrobial resistance (AMR) is a worldwide concern among infectious diseases due to increased mortality, morbidity and treatment cost. According to WHO 2019 report, among the 32 antibiotics in the clinical trials, only six were classified as innovative and containing novel moiety. The remaining antibiotics from this list contain previously known moiety (WHO AMR 2019). Therefore, the development of novel antibiotics to control resistance problems is crucial. Benzothiazole derivatives are of great interest due to their wide range of biological activities and medicinal applications. Reported data indicated that benzothiazole derivatives displayed antibacterial activity by inhibiting the dihydroorotase, DNA gyrase, uridine diphosphate-n-acetyl enol pyruvyl glucosamine reductase (MurB), peptide deformylase, aldose reductase, casdihydrofolate reductase, enoyl acyl carrier protein reductase, dialkylglycine decarboxylase, dehydrosqualene synthase, dihydropteroate synthase and tyrosine kinase. The present review analyzed the synthesis, structure-activity relationship (SAR) and mechanism of action studies of benzothiazole derivatives as antibacterial agents reported by various research groups in the last five years (2018-2022). Different patents on the antimicrobial activity of benzothiazole derivatives have also been summarized. The finding of the present review will be beneficial for the researchers in the development of novel antibacterial molecules based on benzothiazole moiety.

1,3,4-oxadiazole derivatives as potential antimicrobial agents.

Due to the emergence of drug-resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4-Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4-oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non-bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4-oxadiazoles as antimicrobial agents. 1,3,4-oxadiazole derivatives target enoyl reductase (InhA), 14α-demethylase in the mycobacterial cell; GlcN-6-P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450-14α demethylase, protein-N-myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4-oxadiazole derivatives.

Comparison of conventional and non conventional methods of extraction of heartwood of Pterocarpus marsupium Roxb.

The renewed interest in plant-derived drugs has led to an increased need for efficient extraction methods. The present investigation was an attempt to evaluate and compare the conventional methods of extraction with non conventional methods of extraction, such as ultrasonic-assisted extraction (UAE) and microwave-assisted extraction (MAE) methods. Pterocarpus marsupium Roxb. has been reported to contain bioactive phytochemicals, e.g., pterostilbene (3',5'-dimethoxy-4-stilbenol). The results showed that among the conventional extraction methods, percolation gave the highest yield. The non conventional methods were optimized. The extraction yield was the highest in case of MAE. The phytochemical screening of the extracts indicated similar groups of compounds in all the extracts. The thin layer chromatography showed the presence of pterostilbene in the extracts obtained by using percolation, MAE and UAE. In these extracts the quantification of pterostilbene was conducted by high performance liquid chromatography and the method was validated. The MAE method extracted significantly higher amount of pterostilbene.