Structure-activity Relationship Research Articles

Scaled and Weighted Laplacian Matrices as Functional Descriptors for GPCR Ligands.

The G protein-coupled receptor (GPCR) pharmacology accounts for a significant field in research, clinical studies, and therapeutics. Computer-aided drug discovery is an evolving suite of techniques and methodologies that facilitate accelerated progress in drug discovery and repositioning. However, the structure-activity relationships of molecules targeting GPCRs are highly challenging in many cases since slight structural modifications can lead to drastic changes in biological functionality. Numerous molecular descriptors have been described, many of which successfully characterize the structural and physicochemical features of drug sets. Nonetheless, elucidating the structure-functionality relationships over extensive sets of drugs with multiple structural variations and known biological activity remains challenging in various biological systems. This work presents novel topological descriptors using Laplacian matrices, weighted, and scaled by atomic mass and partial charges. We tested these descriptors on three sets of GPCR ligands: muscarinic, β-adrenergic, and δ-opioid receptor ligands, evaluating their potential as functional descriptors of these receptors.

Enantiomer-Dependent Supramolecular Antibacterial Therapy for Drug-Resistant Bacterial Keratitis.

Bacteria have the potential to exhibit divergent stereochemical preferences for different levels of chiral structures, including from molecule, supramolecule, to nanomicroscale helical structure. Accordingly, the structure-activity relationship between chirality and bactericidal activity remains uncertain. In this study, we seek to understand the multivalent molecular chirality effect of chiral supramolecular polymers on antibacterial activity. Two n-butylazobenzene-modified l- and d-tripeptides (abbreviated C4Azo-l-VKK-OH and C4Azo-d-VKK-OH) were synthesized and subsequently self-assembled in water into chiral supramolecular polymers (designated l-Fiber and d-Fiber, respectively). The l-Fiber and d-Fiber displayed comparable nonhelical nanofiber morphologies but exhibited opposite multivalent molecular chirality. A comparative study demonstrated that the l-Fiber exhibited a markedly higher affinity for bacteria, thereby demonstrating significantly enhanced bactericidal efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in comparison to that of the d-Fiber. Following disassembly into monomers via host-guest chemistry, the bactericidal potency of both the l-Fiber and d-Fiber was found to be almost lost, suggesting the multivalent molecular chirality effect. Of note, the l-Fiber exhibited superior efficacy in curing MRSA-infected keratitis in comparison to the d-Fiber. These findings highlight the importance of multivalent molecular chirality in the design and development of chiral supramolecular polymers for antibacterial applications. This research also presents an effective chiral supramolecular antibacterial strategy for the treatment of drug-resistant bacteria-infected keratitis.

1,3,4-Oxadiazole Sulfonamide Derivatives Containing Pyrazole Structures: Design, Synthesis, Biological Activity Studies, and Mechanism Study.

Sulfonamide derivatives have been widely used for pesticide research in recent years. Herein, 1,3,4-oxadiazole sulfonamide derivatives containing a pyrazole structure were synthesized, and their structure-activity relationship was studied. Bioactivity tests showed the remarkable efficacy of most synthesized compounds. Especially for Xanthomonas oryzae pv oryzae, A23 exhibited 100% inhibition at 100 mg/L, surpassing bismerthiazol (99.3%), and 90% inhibition at 50 mg/L, outperforming thiodiazole copper (84.5%), with an EC50 of 5.0 mg/L, markedly more active than bismerthiazol (23.9 mg/L) and thiodiazole copper (63.5 mg/L). Initial investigations into antimicrobial mechanisms involved a series of biochemical analyses, including bacterial growth rate analysis, scanning electron microscopy, bacterial biofilm formation experiments, and molecular docking analyses. Notably, A23 considerably inhibited the formation of Xoo biofilms, disrupting the integrity of bacterial cell membranes. Co-analysis of transcriptomics and proteomics revealed the capability of A23 to regulate pathways such as tryptophan metabolism and phenylpropanoid biosynthesis, enhancing the innate immunity of rice and activating its disease resistance. Thus, A23 emerges as a potential immunoinducible pesticide lead compound for the discovery of highly active immune-inducing agents.

Dynamic regulation of ferroelectric polarization using external stimuli for efficient water splitting and beyond.

Establishing and regulating the ferroelectric polarization in ferroelectric nano-scale catalysts has been recognized as an emerging strategy to advance water splitting reactions, with the merits of improved surface charge density, high charge transfer rate, increased electronic conductivity, the creation of real active sites, and optimizing the chemisorption energy. As a result, engineering and tailoring the ferroelectric polarization induced internal electric field provides significant opportunities to improve the surface and electronic characteristics of catalysts, thereby enhancing the water splitting reaction kinetics. In this review, an interdisciplinary and comprehensive summary of recent advancements in the construction, characterization, engineering and regulation of the polarization in ferroelectric-based catalysts for water splitting is provided, by exploiting a variety of external stimuli. This review begins with a detailed overview of the classification, benefits, and identification methodologies of the ferroelectric polarization induced internal electric field; this offers significant insights for an in-depth analysis of ferroelectric-based catalysts. Subsequently, we explore the underlying structure-activity relationships for regulating the ferroelectric polarization using a range of external stimuli which include mechanical, magnetic, and thermal fields to achieve efficient water splitting, along with a combination of two or more fields. The review then highlights emerging strategies for multi-scale design and theoretical prediction of the relevant factors to develop highly promising ferroelectric catalysts for efficient water splitting. Finally, we present the challenges and perspectives on the potential research avenues in this fascinating and new field. This review therefore delivers an in-depth examination of the strategies to engineer the ferroelectric polarization for the next-generation of water electrolysis devices, systems and beyond.

Development of Potent and Selective CK1α Molecular Glue Degraders.

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation. By scaffold hopping and rational modification of the chemical scaffold, we identified an imidazo[1,2-a]pyrimidine compound that induces potent and selective CK1α degradation. A structure-activity relationship study of the lead compound, QXG-6442, identified the chemical features that contribute to degradation potency and selectivity compared to other frequently observed neosubstrates. The glutarimide library screening and structure-activity relationship medicinal chemistry approach we employed is generally useful for developing new molecular glue degraders toward new targets of interest.

Quinoline and quinolone carboxamides: A review of anticancer activity with detailed structure-activity relationship analysis.

Quinoline is a highly privileged scaffold with significant pharmacological potential. Introducing a carbonyl group into the quinoline ring generates a quinolone ring, which exhibits promising biological properties. Incorporating a carboxamide linkage at different positions within the quinoline and quinolone frameworks has proven an effective strategy for enhancing pharmacological properties, particularly anticancer potency. Consequently, various scientific communities have explored quinoline and quinolone carboxamides for their anticancer activities, introducing modifications at key positions. This review article aims to compile the anticancer activity of various quinoline and quinolone carboxamide derivatives, accompanied by a detailed structure-activity relationship (SAR) analysis. It also categorizes the data into activities of isolated/fused quinoline and quinolone carboxamide derivatives, which were further subclassified based on the mechanisms of anticancer action. Among the numerous derivatives studied, compounds 8, 19, 31, 34, 40, 68, 108, 116, and 132 have emerged as the most potent anticancer agents, making them strong candidates for further drug design and development. The mechanisms underlying the anticancer activity of these potent compounds have been identified as inhibitors of topoisomerase (8, 19, 31, and 34), protein kinase (40, 108, and 116), human dihydroorotate dehydrogenase (68), and as a cannabinoid receptor 2 agonist (132). We anticipate this review will be valuable to researchers engaged in the structural design and development of quinoline and quinolone carboxamide-based anticancer drugs with high efficacy.

Recent Advances in Direct Synthesis of Functional Polymers of Intrinsic Microporosity Based on (Super)Acid Catalysis.

Polymers of intrinsic microporosity (PIMs) are an emerging class of amorphous organic porous materials with solution processability, which are widely used in a multitude of fields such as gas separation, ion conduction, nanofiltration, etc. PIMs have adjustable pore structure and functional pore wall, so it can achieve selective sieving for specific substances. In order to meet the functional requirements of PIMs, two principal methods are used to synthesize functional PIMs, namely, post-modification of PIMs precursors and functionalization of monomers. A number of post-modification routes have been reported, however, the direct synthesis of functional PIMs with diverse groups still remains a challenge. The synthesis of PIMs through the acid-catalyzed polyhydroxyalkylation has been demonstrated to be an effective solution, exhibiting the advantages of wider substrates range, milder reaction conditions, and higher molecular weight. Recently, a series of functional substrates for direct synthesis of PIMs have been proposed. This article presents a review and summary of recent advances in synthesizing PIMs via acid-catalyzed polyhydroxyalkylation, and the synthesis route and structure-activity relationship are emphasized, which provides a versatile platform for the direct synthesis of functional PIMs.

Molecular Modeling Studies and Synthesis of Isocryptolepine Derivatives as Antimalarial Using Docking, CoMFA, CoMSIA, and HQSAR.

Our research highlights the synthesis of newer antimalarial compounds using molecular modeling studies. The study investigates a series of isocryptolepine derivatives from previous literature, focusing on their biological activities as antimalarial agents. Computational methods such as molecular docking and QSAR were employed to gain insights into the interaction between the synthesized compounds and the target enzyme PfDHFR-TS. Molecular docking studies helped to identify key binding interactions, supporting the design of more effective compounds. Using CoMFA and CoMSIA, the study explored steric, electrostatic, and hydrogen-bonding fields, providing a quantitative structure-activity relationship (QSAR) for 49 compounds. The CoMFA model yielded strong predictive r² values of 0.971, while the CoMSIA model highlighted the significance of hydrophobic and hydrogen bond interactions. These findings inform the design of novel isocryptolepine derivatives with improved antimalarial activity.

Isolated Metal Centers Activate Small Molecule Electrooxidation: Mechanisms and Applications.

Electrochemical oxidation of small molecules shows great promise to substitute oxygen evolution reaction (OER) or hydrogen oxidation reaction (HOR) to enhance reaction kinetics and reduce energy consumption, as well as produce high-valued chemicals or serve as fuels. For these oxidation reactions, high-valence metal sites generated at oxidative potentials are typically considered as active sites to trigger the oxidation process of small molecules. Isolated atom site catalysts (IASCs) have been developed as an ideal system to precisely regulate the oxidation state and coordination environment of single-metal centers, and thus optimize their catalytic property. The isolated metal sites in IASCs inherently possess a positive oxidation state, and can be more readily produce homogeneous high-valence active sites under oxidative potentials than their nanoparticle counterparts. Meanwhile, IASCs merely possess the isolated metal centers but lack ensemble metal sites, which can alter the adsorption configurations of small molecules as compared with nanoparticle counterparts, and thus induce various reaction pathways and mechanisms to change product selectivity. More importantly, the construction of isolated metal centers is discovered to limit metal d-electron back donation to CO 2p* orbital and reduce the overly strong adsorption of CO on ensemble metal sites, which resolve the CO poisoning problems in most small molecules electro-oxidation reactions and thus improve catalytic stability. Based on these advantages of IASCs in the fields of electrochemical oxidation of small molecules, this review summarizes recent developments and advancements in IASCs in small molecules electro-oxidation reactions, focusing on anodic HOR in fuel cells and OER in electrolytic cells as well as their alternative reactions, such as formic acid/methanol/ethanol/glycerol/urea/5-hydroxymethylfurfural (HMF) oxidation reactions as key reactions. The catalytic merits of different oxidation reactions and the decoding of structure-activity relationships are specifically discussed to guide the precise design and structural regulation of IASCs from the perspective of a comprehensive reaction mechanism. Finally, future prospects and challenges are put forward, aiming to motivate more application possibilities for diverse functional IASCs.

Flavonoids as Potential Modulators of Pancreatic Lipase Catalytic Activity

Background/Objectives: Obesity has reached pandemic proportions, with predictions suggesting that, by 2030, over 1.5 billion people will be affected. Pancreatic lipase (PL), the enzyme primarily responsible for the absorption of dietary lipids, presents a potential target for obesity management. However, while porcine pancreatic lipase (PPL) is commonly used as the enzyme source for screening potential inhibitors, its effect on human pancreatic lipase (HPL) is rarely reported. This work aimed to screen the inhibitory effects of a library of flavonoids with different functional groups on the activity of PL from the human pancreas (triacylglycerol acyl hydrolase, EC 3.1.1.3) and compare it to the effects of the porcine pancreas (type II, EC 3.1.1.3), establishing, whenever possible, a structure–activity relationship. Methods: The inhibitory effects of a library of 48 flavonoids with different hydroxy, glycosyl, rutinosyl, galloyl, and extended alkyl groups were evaluated against PPL and HPL. The kinetic parameters and inhibitory mechanisms of the most active flavonoids were determined, and in silico docking studies of the more potent flavonoids were also performed, using the active site of HPL. Results/Conclusions: Variations in enzyme catalytic activity were observed depending on the source of the enzyme. The inhibitory effect was particularly influenced by the presence of extended alkyl groups at the C-3 of the C-ring and the C2=C3 double bond of the C-ring and the presence of a pyrogallol group at the C-2′, C-3′ and C-4′ of the B-ring. Docking results showed a strong correlation between docking scores and observed inhibitory activities, highlighting the critical role of specific substituents on the flavonoid backbone in enhancing detailed interaction dynamics with key amino acids. Compounds 28, 29, and 30, with alkyl groups, showed the highest docking scores, interacting with residues HIS151, PHE215, ARG256, and HIS263. Further analysis also revealed that specific substituents improved pocket occupancy and formed additional interactions with residues TYR114, PRO180, ILE209, and PHE215, which are crucial for inhibition. These binding characteristics closely mimic those observed with orlistat, reinforcing their mechanistic similarities in inhibiting HPL and validating their inhibitory activities.

Advances in cyclotide research: bioactivity to cyclotide-based therapeutics.

Cyclotides are a class of plant-derived cyclic peptides having a distinctive structure with a cyclic cystine knot (CCK) motif. They are stable molecules that naturally play a role in plant defense. Till date, more than 750 cyclotides have been reported among diverse plant taxa belonging to Cucurbitaceae, Violaceae, Rubiaceae, Solanaceae, and Fabaceae. These native cyclotides exhibit several bioactivities, such as anti-bacterial, anti-HIV, anti-fungal, pesticidal, cytotoxic, and hemolytic activities which have immense significance in agriculture and therapeutics. The general mode of action of cyclotides is related to their structure, where their hydrophobic face penetrates the cell membrane and disrupts it to exhibit anti-microbial, cytotoxic, or hemolytic activities. Thus, the structure-activity relationship is of significance in cyclotides. Further, owing to their, small size, stability, and potential to interact and cross the membrane barrier of cells, they make promising choices for developing peptide-based biologics. However, challenges, such as production complexity, pharmacokinetic limitations, and off-target effects hinder their development. Advancements in cyclotide engineering, such as peptide grafting, ligand conjugation, and nanocarrier integration, heterologous production along with computational design optimization, can help overcome these challenges. Given the potential of these cyclic peptides, the present review focuses on the diversity, bioactivities, and structure-activity relationships of cyclotides, andadvancements in cyclotides engineering emphasizing their unique attributes for diverse medical and biotechnological applications.

Discovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies.

Inhibition of the adenosine 2A receptor (A2AR) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of A2AR function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel A2AR NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives. The allosteric mode of action of active compounds was confirmed by progressive fold-shift assay, nonlinearity of the Schild plot analysis, biophysical measurements, and retained satisfactory potencies in high-adenosine concentrations. Further correlation of A2AR engagement and downstream signaling was done in a human blood translational assay, clearly showcasing the potential of A2AR allosteric modulation as a novel approach for efficient and safer cancer immunotherapies.

Molecular Docking Study and 3D-QSAR Model for Trans-Stilbene Derivatives as Ligands of CYP1B1

Scientific research on stilbenes is conducted for their chemopreventive and therapeutic properties. In experimental studies, natural and synthetic trans-stilbenes exhibit antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. The antitumor activity of some natural and synthetic stilbenes is associated with their interaction with cytochrome P450 family 1, which leads to the inhibition of procarcinogen activation. In the present study, three-dimensional quantitative structure–activity relationship analysis (3D-QSAR) was performed on a series of forty-one trans-stilbene derivatives to identify the most significant features of the molecules responsible for their CYP1B1 inhibitory activity. The developed 3D-QSAR model presented a cross-validated correlation coefficient Q2 of 0.554. The model’s predictive ability was confirmed by external validation (r2 = 0.808). The information provided by 3D-QSAR analysis is expected to be valuable for the rational design of novel CYP1B1 inhibitors.

Scalable preparation of furanosteroidal viridin, β-viridin and viridiol from Trichoderma virens

Viridin and viridiol, along with wortmannin, metabolized by filamentous fungus Trichoderma virens, are identical furanosteroids with high-potent inhibitory activity towards phosphatidylinositol 3-kinase (PI3K) that associates the growth of tumor cells. Therefore, structure–activity relationship study (SAR) of these furanosteroids contributes to the development of novel drugs. However, rational supply methods have not been established yet. In this study, we generated an efficient method to produce both viridin and viridiol by using a unique pH regulated T. virens culture manner. Besides, we successfully obtained β-viridin (epimer of viridin) crystal and X-ray structure, of which the CAS number was registered without stereochemistry. Furthermore, applying the original method to stable isotope study, we also obtained [U-13C]-viridn and [U-13C]-viridol by using [U-13C6]-glucose as a carbon source replacing normal glucose which can be used to elucidate the biosynthesis pathway of furanosteroids.

A (Comprehensive) Review of the Application of Quantitative Structure–Activity Relationships (QSARs) in the Prediction of New Compounds with Anti-Breast Cancer Activity

Computational approaches applied in drug discovery have advanced significantly over the past few decades. These techniques are commonly grouped under the term “computer-aided drug design” (CADD) and are now considered one of the key pillars of pharmaceutical discovery pipelines in both academic and industrial settings. In this work, we review Quantitative Structure–Activity Relationships (QSARs), one of the most used ligand-based drug design (LBDD) methods, with a focus on its application in the discovery and development of anti-breast cancer drugs. Critical steps in the QSAR methodology, essential for its correct application—but often overlooked, leading to insignificant or misleading models—are examined. Additionally, current anti-breast cancer treatment strategies were briefly overviewed, along with some targets for future treatments. The review covers QSAR studies from the past five years and includes a discussion of notable works that could serve as models for future applications of this interdisciplinary and complex method and that may help in feature drug design and development.

Design, synthesis, anti-inflammatory evaluation, and molecular docking studies of novel quinazoline-4(3H)-one-2-carbothioamide derivatives.

In this paper, a series of novel quinazoline-4(3H)-one-2-carbothioamide derivatives (8a-p) were designed and synthesized via the Wilgerodt-Kindler reaction between 2-methylquinazoline-4-one 10 and amines using S8/DMSO as the oxidizing system. Their characteristics were confirmed by IR, NMR, HRMS spectra, and their melting point. These novel derivatives (8a-p) were evaluated for their anti-inflammatory activity by inhibiting NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells. Compounds 8d (IC50 = 2.99 μM), 8g (IC50 = 3.27 μM), and 8k (IC50 = 1.12 μM) exhibited potent inhibition of NO production compared to the standard drug dexamethasone (IC50 = 14.20 μM). Compound 8a (IC50 = 13.44 μM) exhibited NO inhibition comparable to dexamethasone. Structure-activity relationship (SAR) studies indicated that the presence of both the thioamide functional group (NH-C[double bond, length as m-dash]S) directly attached to the phenyl ring containing halogen substituents (4-Cl, 8d), (4-Br, 8g) and (4-CF3, 8k), is responsible for the potent anti-inflammatory activity of these novel quinazolinone derivatives. Computational modeling studies revealed that compounds 8d, 8g, and 8k are potent inhibitors of TLR4 signaling through the formation of hydrophobic interactions and are stabilized by hydrogen bonds. Replacing the thioamide (8k) with an amide (8q) resulted in an 83-fold decrease in NO inhibitory potency. This highlights the important role of H-bonding involving the thioamide group. The structural shape difference results in favorable interactions of quinazolinones containing thioamide linkers compared to amide linkers to the target receptor. Furthermore, the ADMET profiles and physicochemical properties of these three lead compounds were predicted to meet the criteria for drug-like properties. Therefore, these compounds may be potential candidates for the treatment of many inflammatory diseases associated with immune disorders.

Quantitative structure-activity relationship (QSAR) hazard assessment of the banned pesticides by the National Agency for Food and Drugs Administration and Control.

This study carried out a quantitative structure-activity relationship hazard assessment of the banned pesticides in Nigeria with a view of identifying the dangers posed by these pesticides. Structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), which link a compound's chemical structure to its biological activity, can be used to create safer and more effective insecticides, prioritize chemicals for testing, and reduce the number of animal studies necessary throughout the regulatory process. The QSAR hazard assessment of the banned pesticides was carried out on the VEGA software. Environmental, (eco)toxicological, reproductive/developmental, body elimination half-life, and biodegradability models of human and ecological relevance were implemented within the VEGA software. The results predicted the different hazards associated with each of the banned pesticides. All of the banned pesticides have been predicted to be toxic to some or all of the evaluated endpoints. The studies predicted these pesticides to have potential of being mutagenic, carcinogenic, and/or toxic to the reproductive system and fetal development with different half-lives. The assessment further predicted most of these compounds to be non-biodegradable with tendencies to bioaccumulate in living things and the environment. It can be concluded that these pesticides have potential to cause harm to life and the environment. The use of these chemical compounds for domestic, industrial, and agricultural applications should be in accordance with the guideline of regulatory agencies.

Chemical structure-biological activity of 1,4-naphthoquinone analogs as potential Aedes aegypti larvicides.

1,4-Naphthoquinone compounds have shown pesticidal activity against Aedes aegypti larvae, a key vector of diseases such as dengue and Zika. However, limited knowledge of their structure-activity relationships has hindered their optimization for pesticide development. This study investigates the structure-activity relationships of 1,4-naphthoquinone, particularly 2-hydroxy-1,4-naphthoquinone and its derivatives. A series of 1,4-naphthoquinones with modifications at the C-2, C-5, and C-8 positions were synthesized and tested for larvicidal activities against Ae. aegypti. The presence of chlorine substituents at the C-2 position significantly increased mosquito larval mortality. In contrast, 2-hydroxy and 2-methoxy groups were less effective, highlighting the importance of the C-2 substituent in determining larvicidal activity. The compounds were tested on both pyrethroid-susceptible Orlando 1952 (ORL1952) and permethrin-resistant Puerto Rico (PR) strains of Ae. aegypti. While compound 1d exhibited the lowest median lethal concentration (LC50) against ORL1952 larvae, it showed minimal activity against the PR strain, which is resistant. The most promising compounds, 1 and 4a, showed LC50 values of 2.764 and 4.916 ppm in the ORL strain, and 2.548 and 4.878 ppm in the PR strain, respectively. Chlorine substitution at the C-2 position of 1,4-naphthoquinones enhances larvicidal activity against Ae. aegypti, while 2-hydroxy and 2-methoxy substitutions reduce efficacy. Certain compounds, such as 1 and 4a, show potential as broad-spectrum agents effective against both susceptible and resistant strains of Ae. aegypti, highlighting their promise for further development as mosquito control agents. © 2025 Society of Chemical Industry.

Novel isoxazole thiophene-containing compounds active against Mycobacterium tuberculosis.

Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC50 = 1.96 µM and exhibited 58.0 % oral bioavailability when it was dosed orally at 20 mg/kg in a mouse pharmacokinetic (PK) study. The overall medicinal chemistry campaign revealed limited SAR that did not support further investigation into this series.

Exploring 1-Azaaurones: A Concise Overview of Synthetic Strategies and Biological Activities.

Azaaurones are formed by the replacement of intra-cyclic oxygen of the central core of a five-membered furan ring or any other carbon of aurones by a nitrogen atom. However, 1- azaaurone obtained by the replacement of intra-cyclic oxygen is the most prominent and desirable. They are the bioactive compounds acting as potential anti-inflammatory, anticancer, antibacterial, and antiviral agents. They comprise relatively less explored, pharmacologically active compounds exhibiting diverse biological activities that can act as potential lead compounds in the context of drug development. This review represents a comprehensive and updated overview of the synthetic protocols and biological activities of 1-azaaurones and their derivatives, enabling the readers to know about the vast medicinal potential of azaaurones and their derivatives in different areas and prompt the medicinal chemists to emphasize their further exploration. Furthermore, this review also covers some important Structure-Activity Relationships (SAR), highlighting the most potential compounds in each series, providing pivotal scope for further improvisation.