Future medicinal chemistry最新文献

Organoselenium chemistry has become a significant field due to its role in synthesizing numerous biologically active and therapeutic compounds. In early phase, researchers focused on designing organoselenium compounds with antioxidant properties and were quite successful. In last two decades, synthetic chemists shifted their focus toward synthesis of organoselenium compounds with biological properties, moving beyond their traditional antioxidant properties. The review includes synthesis and study of organo-selenium compounds as anticancer, antimicrobial, antiviral, antidiabetic, antithyroid, anti-inflammatory therapies, contributing to disease treatment. This review covers the synthesis and medicinal applications of synthetic organoselenium compounds over the past 10 years, thus making it a valuable resource for researchers in the field of medicinal chemistry.

Aim: New pyrano[3,2-c]pyridine 4a-h, 5-8 and pyrano[2,3-d]pyrimidin 9a,b series were designed and chemically synthesized.

Methodology: Using the standard drug doxorubicin, the novel chemical entities have been assessed in vitro as potential anticancer prospects on cell lines from liver, breast, colon, and lung cancer along with examining their inhibitory behaviors upon both EGFR and VEGFR-2 kinases.

Results & conclusion: Compared to erlotinib (IC₅₀ = 0.18 µM), compounds 8a and 8b demonstrated the highest anticancer activity with IC₅₀ Values 0.23 and 0.15 µM, respectively). Further, derivative 8a illustrated encouraging inhibitory characteristics against EGFR and VEGFR-2 (IC₅₀ = 1.21 and 2.65 μM, respectively). A computational study was used to estimate the physicochemical and pharmacokinetic properties to afford insightful information about the newly synthesized agents.

Aims: Current research work aims to synthesize hybrid compounds with a thiazole-thiazolidinone structure, as potent inhibitors of urease and α-glucosidase enzymes.

Materials and methods: These compounds were characterize through¹HNMR,¹³CNMR and HREI-MS techniques. These compounds were also evaluated for their potential to inhibit urease and α-glucosidase enzymes for the treatment of urinary tract infections (UTIs) and diabetes treatments. Moreover, molecular docking and ADMET analysis was carried out to confirm biological outcomes.

Results and conclusion: Compounds-4 (IC₅₀ = 1.80 ± 0.80 and 3.61 ± 0.59 μM against urease and α-glucosidase, respectively) exhibited significant effectiveness in inhibiting the activity of both enzymes in comparison to the conventional inhibitors thiourea and acarbose. Molecular docking experiments showed that potent compounds exhibited favorable binding orientations in the active sites of urease and α-glucosidase playing a pivotal role in inhibition profile of these compounds. These compounds were also investigated for their drug likeness and were found with desirable attributes for pharmaceutical development. Based on the findings of this research, these compounds have the potential to be developed into effective anti-diabetic and anti-urease treatments in the future.

Aim: To develop a model for predicting the biological activity of compounds targeting the HIV-1 protease and to establish factors influencing enzyme inhibition.Materials & methods: Machine learning models were built based on a combination of Richard Bader's theory of Atoms in Molecules and topological analysis of electron density using experimental x-ray 'protein-ligand' complexes and inhibition constants data.Results & conclusion: Among all the models tested, logistic regression achieved the highest accuracy of 0.76 on the test set. The model's ability to differentiate between less active and highly active classes was relatively good, as indicated by an AUC-ROC score of 0.77. The analysis identified several critical factors affecting the biological activity of HIV-1 protease inhibitors, including the electron density contribution of hydrogen atoms, bond-critical points and particular amino acid residues. These findings provide new insights into how these molecular factors influence HIV-1 protease inhibition, emphasizing the importance of hydrogen bonding, glycine's flexibility and hydrophobic interactions in ligand binding.

Background: Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery.Aim: Development of novel nicotinamides as VEGFR-2 inhibitors.Methods: different in vitro and in silico assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.Results: Compound 16c displayed strongest anti-VEGFR-2 potentiality and good anti-proliferative effects. Compound 16c enhanced apoptosis and caused cell cycle arrest in the Pre-G1 and S phases. Compound 16c boosted the level of the apoptotic caspase-3 and inhibited the level of TNF-α and IL-6 in tumor cells. Molecular docking and molecular dynamics (MD) simulations indicated the outstanding binding potential of compound 16c against VEGFR-2.Conclusion: Compound 16c is a good candidate for the creation of a novel antiangiogenic lead anticancer medication.