INTRODUCTION
Inflammation and oxidative stress play important roles in the development of various chronic diseases, necessitating compounds with dual therapeutic potential.
METHODS
A series of (E)-7-hydroxy-4-methyl-6-(3-(substituted phenyl)acryloyl)-2H-chromen-2-one (7a-m) were synthesized starting from 7-hydroxy-4-methyl coumarin. The synthesized compounds were evaluated for their in vitro antioxidant and anti-inflammatory activity Results: Compound 7a exhibited the most potent antioxidant activity with an IC50 value of 83.39 μM. Compound 7b was found to be nearly 1.5-fold more potent in inhibiting albumin protein denaturation than ibuprofen and diclofenac at 100 μg/ml. Compound 7b displayed the most potent inhibitory activity against TNF-α and weak inhibition against the COX-2 enzyme with an IC50 value of 4.32 and 419.04 μM, compared to standard ibuprofen (IC50 value of 5.0 μM against COX-2) and diclofenac (IC50 value of 21.0 μM against TNF-α). Molecular docking studies of compound 7b showed the highest docking score against TNF-α and COX-2 enzymes, compared to the standard celecoxib.
DISCUSSION
It was found that chloro at the 2nd position or methoxy at the 3rd position led to promising anti-inflammatory activity. Removal of the chloro group led to a decrease in COX-2 and TNF-α inhibitory activity. In the molecular docking studies, compound 7b shows a similar binding interaction against TNF-α and COX-2 as the standard celecoxib. The DFT studies showed favorable interactions, good stability, and moderate reactivity within the biological targets.
CONCLUSION
Based on the results of the present study, it is suggested that coumarin-chalcone derivatives may act as a lead for the synthesis of more potent antioxidants and anti-inflammatory compounds.
Dalaa Ali El-Jadayel, Husna Khalifa Al-Busaidi, Zainab Hamood Al-Balushi et al.· Anti-Inflammatory & Anti-All...· 0 citations
Abstract The rhodanine core or 2-thioxothiazolidin-4-one, a five-membered heterocyclic ring system, has garnered significant interest in drug discovery, owing to its diverse biological activities. Derivatization of rhodamine has yielded many clinically useful therapeutic compounds for various ailments due to the presence of both nitrogen and sulfur heteroatoms within its ring system. Its broad-spectrum activities are facilitated by its two key electrophilic binding groups, ketone and thioketone, which enable interactions with various biological targets. Significant advances have been made toward its efficient synthetic strategies for drug discovery and development. This comprehensive review discusses rational design strategies for rhodanine-based heterocycles and their therapeutic potential as antibacterial, anti-diabetes, anti-Alzheimer’s, anticancer, anthelmintic, anti-obesity, and against COVID-19. The article also sheds light on the synthetic strategies used to develop rhodamine derivatives and drug design supported with detailed structure-activity relationships (SAR). Further molecular docking providing mechanistic insights into their binding modes within receptors are also presented. These structural insights could help in further rational design of potent rhodamine derivatives as newer and safer therapeutic agents. Graphical AbstractCentral yellow molecular structure linked to various disease icons: anticancer, antibacterial, anti-Alzheimer, anti-COVID-19, antidiabetic, and anthelmintic.The diagram presents a central yellow molecular structure with elements like nitrogen (N), sulfur (S), and oxygen (O). It illustrates connections to diverse biological applications: anticancer, antibacterial, anti-Alzheimer, anti-COVID-19, antidiabetic & anti-obesity, and anthelmintic, represented by icons in surrounding circles. A curved green line labeled "Structure Activity Relationship" encircles the categories. Above, a labeled 'Drug Design' oval and precursor molecules R-NH2, ClCH2COOH, and CS2 are included, visually connecting the drug synthesis process and biological targets.
R. Nath, Lakshminarayan Das, Arka Chakraborty et al.· Phosphorus Sulfur and Silico...· 0 citations
Heterocyclic scaffolds are vital to medicinal chemistry due to their versatility, diversity, and ability to target various biological molecules. This review covers advances in designing and synthesizing bioactive heterocycles, highlighting structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches with computational modeling and Artificial Intelligence (AI) to find potent, selective molecules with good Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profiles. Case studies show the successful development of heterocyclic drugs for cancer, microbial infections, inflammation, viral infections, and Central Nervous System (CNS) disorders. Synthetic methods have evolved from classical electrophilic/nucleophilic reactions to modern techniques like multicomponent reactions, microwave synthesis, metal catalysis, and green chemistry, making frameworks more accessible. The review discusses Quantitative Structure-Activity Relationship (QSAR) studies for molecular optimization. Challenges like synthetic complexity and resistance remain, but emerging trends like machine learning, omics, and enzyme synthesis offer new opportunities. Ultimately, combining design principles and innovative methods can speed up drug discovery and enable sustainable, personalized therapies with heterocyclic pharmacophores.
Debajit Dewan, Bhupender Nehra, R. Nath et al.· Future Medicinal Chemistry· 0 citations
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