The development of soluble epoxide hydrolase (sEH) inhibitors has emerged as a promising therapeutic strategy, yet progress has been constrained by structural similarity and suboptimal pharmacokinetic profiles. While numerous synthetic and natural product-derived inhibitors demonstrate potent pharmacological activity, their clinical translation has been hampered by recurring limitations including poor solubility, low AUC, CYP inhibition, and hERG toxicity. This review critically evaluates recent breakthroughs in scaffold diversification and rational design approaches that overcome these limitations. We highlight innovative synthetic methodologies, structure-activity relationship insights, and novel chemotypes that expand the chemical space beyond conventional urea-based scaffolds. Furthermore, we discuss emerging therapeutic applications enabled by these advanced inhibitors, providing a strategic roadmap for next-generation sEH-targeted drug discovery.

Understanding protein-ligand binding site behavior is central to structure-based drug design. We analyzed amino acid composition and interactions in protein-ligand small-molecule binding sites and developed a novel method for binding site prediction.

One of the main therapeutic approaches to prevent symptoms and slow the progression of Alzheimer's disease (AD) is cholinesterase inhibitors. For this purpose, some novel 2-pyrazoline-1-carboxamide derivatives based on cuminaldehyde were synthesized.

To synthesize and characterize vanillin-mediated hydrazine derivatives (1a-j) and evaluate their in vitro antibacterial, antioxidant, and cytotoxic activities. This study is further supported by molecular docking, MD simulation, and DFT calculation studies.

Malaria causes major mortality, with the downward trend in the number of cases and deaths seemingly stalled. In 2023, 95% of global malaria deaths were reported in the World Health Organization (WHO) African region, with children under the age of 5 years being the most affected. Artemisinin-combination therapies (ACTs), the currently recommended first-line treatments, are threatened by resistance, which has so far been reported in Africa and Southeast Asia. Thus, new drugs are needed.

Antimicrobial resistance remains a critical global health threat, driving the urgent need for novel therapeutic agents. Cannabinoids, bioactive secondary metabolites derived from , have gained attention for their promising antimicrobial properties. This review presents the latest advances in the antimicrobial properties of cannabinoids, emphasizing their activity against multidrug-resistant pathogens, including methicillin-resistant , vancomycin-resistant , and selected Gram-negative bacteria. We summarize their antibacterial and antifungal effects, along with insights into structure-activity relationships that reveal the critical roles of functional groups such as the resorcinol moiety and alkyl side chain. Mechanistic studies suggest that membrane disruption, metabolic interference, and reactive oxygen species generation contribute to their antimicrobial action. Moreover, we summarize the synergistic potential of cannabinoids when used in combination with conventional antibiotics, highlighting both promising outcomes and notable limitations. Despite these advances, challenges such as poor solubility, limited in vivo data, and regulatory barriers persist. Addressing these gaps through focused medicinal chemistry and translational research will be essential to harness the full potential of cannabinoids as next-generation antimicrobial agents.

Novel heterocyclic analogs with dual antibacterial and anticancer potential were synthesized to address the limitations posed by multidrug resistance and current therapies.

This study aimed to design and synthesize novel dehydroacetic acid (DHA) based pyrazole - pyridine conjugates and evaluate their potential efficacy in combating inflammation and malaria.

New pyrazole and 1,3-thiazolyl-pyrazole derivatives were prepared in high yields.

The triazolopyrazine scaffold is characterized by fused triazole and pyrazine rings. It represents a highly versatile, nitrogen-rich heterocyclic framework extensively explored as a prominent scaffold that is of greater importance for developing novel drugs with various biological activities because they may present several structural alterations with identical numbers of carbon and nitrogen atoms. The triazolopyrazine scaffold has broad-spectrum biological activities, including antimalarial, anticancer, antidiabetic, antimicrobial, antifungal, antiviral, and neurological activity. As a result, numerous investigators have synthesized these compounds as target structures and assessed their biological activities. Its broad biological profile has always been a subject of interest, attracting researchers to investigate the distinctive features of this skeleton. In recent years, remarkable progress has been made in the medicinal chemistry of triazolopyrazine-based derivatives. The current review aims to provide research progress on triazolopyrazine hybrids, including structure-activity relationship (SAR) and target interaction analysis, which will pave the way for the design and development of new, novel target-selective triazolopyrazine derivatives as promising agents. This versatile and structurally unique framework of triazolopyrazine scaffold will benefit researchers and medicinal chemists engaged in exploring the triazolopyrazine scaffold as a future lead for drug design and discovery.

This study aimed to evaluate the α-glucosidase inhibitory potential of newly synthesized aurone derivatives (1-14) using an integrated experimental and computational strategy, with emphasis on their antidiabetic potential.

The chalcone scaffold pyrazole is important in organic and medicinal chemistry. This study presents the design and synthesis of new chalcone-coupled pyrazole derivatives (1a-1o). The new compounds were characterized using FT-IR, H-NMR, C-NMR, GC-MS, elemental analysis, and cytotoxic analysis on MCF-7 and HepG2 cancer cell lines. The synthesized compounds also underwent molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity), and DFT (density functional theory) studies.

Natural products (NPs) have long provided privileged scaffolds for drug discovery, yet their biosynthetic restrictions limit exploration of broader natural product chemical space. Pseudo-natural products (pseudo-NPs) have emerged as a promising strategy to overcome these limitations by recombining biosynthetically unrelated natural product fragments into unprecedented frameworks. These scaffolds retain NP-inspired features while extending into novel structural and functional space, often leading to bioactivities not achievable with classical derivatives. This review summarizes recent advances in pseudo-NP design, highlighting fragment selection, connectivity principles, cheminformatic evaluation, and the role of phenotypic profiling, particularly the cell painting assay (CPA), in functional annotation and mode-of-action elucidation. Representative scaffolds, including indotropanes, apoxidoles, pyrano-furo-pyridones, and pseudo-rutaecarpines, are discussed in the context of antiproliferative, anti-inflammatory, antibacterial, and autophagy-related activities. While only a few groups worldwide currently explore this field, the collective evidence underscores the translational promise of pseudo-NPs. Future progress will depend on broader scientific engagement, in vivo validation, and the expansion of fragment diversity to inspire the next generation of therapeutic agents.

A novel series of oxadiazole-based derivatives was designed and synthesized as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors.

Diabetes mellitus develops because of the disturbance in carbohydrate metabolism. The therapeutic goal for antidiabetic medications is to manage blood glucose level and to prevent hyperglycemia-associated complications. α-Glucosidase inhibitors represent one of the widely used oral hypoglycemics. This review highlights the potential of 1,2,4-triazole-containing synthetic molecules as antidiabetic agents, particularly focusing on their α-glucosidase inhibitory activity. It argues the significance of targeting α-glucosidase in managing type 2 diabetes and presents recent synthetic approaches for synthesizing 1,2,4-triazole derivatives. The mechanisms of action, SAR analysis, and docking insights are summarized for various reported 1,2,4-triazoles between 2020 and 2025. A comparative analysis was conducted to identify the most effective methodology and the best starting material for the synthesis of this class. Relative potencies and drug likeness characteristics of the reviewed candidates were also evaluated to identify whether one deserves forwarding to pre-clinical and clinical assessments. Many of these derivatives exhibited potent α-glucosidase enzyme inhibition, often outperforming standard marketed drugs like Acarbose. The review paves the way for medicinal chemists to develop new 1,2,4-triazole-incorporating molecular entities to build safe and effective agents for diabetes treatment.

Despite advances in cancer therapy, tumor aggressiveness remains a challenge due to rapid progression and genetic variability. Tumor cells often overexpress glucose transporters (GLUTs) and receptors such as galectin and ASGP-R. Based on this, new chalcone derivatives conjugated to D-glucose, D-galactose, and lactose were synthesized from a previously identified cytotoxic chalcone (compound 1) to evaluate their anticancer potential.

This study aimed to synthesize and evaluate novel furan derivatives as potential anticancer agents targeting colon cancer through VEGFR-2 inhibition and apoptosis induction.

Urease is essential to metabolism and plays role in stomach cancer, gastritis, peptic ulcer, hepatic coma, urinary tract infection, liver encephalopathy, and pyelonephritis. Therefore, inhibition of urease is an appealing approach to treat bacterial infections.

To design, synthesize, and evaluate a series of thiosemicarbazone and thiazolidin-4-one hybrids bearing arylsulfonate groups as potential androgen receptor-targeted anticancer agents.

The discovery of novel compounds as potential cancer drug candidates has garnered significant interest and widespread attention.

Carbocycles have been widely employed in the development of pharmaceutically active scaffolds. Cyclopropane has attracted significant attention from researchers due to its unique chemical properties among carbocycles. Subsequently, this review will focus on cyclopropane-containing pharmaceutical drug products that have been approved by the FDA (Food and Drug Administration) and are used to treat a wide variety of medical conditions. In addition to the synthesis of the cyclopropyl moiety through various chemical reactions, such as the Corey-Chaykovsky reaction and the Simmons-Smith reaction. Several cyclopropane-containing pharmaceutical drugs have been reported to exert significant anti-coagulant effects. Additionally, they also exhibit inhibitory activity against MET, a receptor tyrosine kinase, as well as vascular endothelial growth factor receptor 2 (VEGFR-2). Moreover, they showed cytotoxicity by inhibiting epidermal growth factor receptor (EGFR). In addition to antidiabetic, anti-Alzheimer, antimalarial, antimicrobial, anti-convulsant and anti-depressant activities. Herein, we present the pharmaceutical applications of cyclopropane-containing derivatives, shedding light on the structure-activity relationship (SAR), along with some commonly reported methods for their synthesis.