ChemistrySelect最新文献

Cancer is highlighted as one of the deadliest diseases globally, with CDK5 identified as a key enzyme in cancer progression. Despite its potential as a therapeutic target, developing CDK5 inhibitors has been challenging. We used multicomplex-based pharmacophore modeling on CDK5 complexes, identifying hydrophobic groups, hydrogen bond donors, and acceptors as crucial inhibition features. Validated models were used for the virtual screening of drug-like natural product databases. Thereafter, the screened candidates were selected to study their binding pattern and binding efficiency in the enzyme. Four molecules were shortlisted and analyzed for electrostatic potential (ESP) energy maps. Molecular dynamic simulations and free energy calculations on the docked complexes revealed stable behavior for all, with three (CNP0299652, CNP0362830, and CNP0009633) showing higher Poisson Boltzmann surface area continuum solvation (MM-PBSA) binding scores than the reference. These candidates demonstrated drug-like characteristics, crucial amino acid interactions, favorable electron potentials in ESP plots, stable dynamicigher free energy, highlighting their potential as CDK5 inhibitors.

Chitosan nanoparticles (ChNP) represent an interesting technological platform for drug delivery to the skin due to their mucoadhesive, nontoxic, and biodegradable characteristics, offering advantages in bypassing the stratum corneum and improving drug delivery in dermal administration. This systematic review analyzed the in vivo applicability of ChNP as a substance delivery system to the skin. A literature search was conducted in the databases PubMed, SciELO, and Lilacs using the keywords “nanoparticle,” “chitosan,” and “skin.” Inclusion criteria involved in vivo studies investigating the effects of topical use of these nanoparticles, published between 2013 and 2023, and comparing the nanoparticulate formulation with the free drug. The prevalence of studies conducted on animal models was 94.1%, while only 5.9% were performed on humans. The results suggest that ChNP formulations improved the delivery of therapeutic agents and demonstrated superior efficacy compared to formulations containing the free drug; they exhibited good permeability and tolerability, gradual release of the active molecule, and faster results with minimal adverse effects. Therefore, ChNP containing active substances for topical application emerges as a safe and effective platform with significant potential for drug delivery to the skin, opening new perspectives for their use in innovative formulations.

1,4-Dihydropyridines (1,4-DHPs) represent a versatile class of organic compounds derived from pyridines, recognized for their extensive synthetic applications and significant medical significances. Among the various synthetic methodologies available, the Hantzsch dihydropyridine synthesis is particularly notable as it provides a reliable approach to the production of these compounds. Recent advancements have markedly improved the synthetic pathways leading to Hantzsch dihydropyridines and their derivatives. This review aims to thoroughly examine the recent progress in the synthesis of 1,4-DHPs, 1,8-dioxodecahydroacridines (AD), and polyhydroquinolines (PHQ). Emphasis is placed on novel synthetic strategies reported in recent years, specifically those that employ multicomponent reactions involving aldehydes, β-ketoesters, and ammonium salts. Furthermore, these reactions are catalyzed by various nanocatalysts, including magnetic nanoparticles, nanocomposites, metal oxides, functionalized nanoparticles, and other environmentally friendly nanobiomaterials. The application of nanocatalysts in these processes is underscored by their contributions to structural integrity and activity enhancement, indicative of a paradigm shifts towards more sustainable and efficient synthetic methodologies. This review consolidates and assesses various synthetic routes facilitated by nanocatalysts while elucidating their distinct roles in improving the efficiency and selectivity of 1,4-DHP synthesis. Hence, this review may pave the way for advancements in Hantzsch reactions by employing nanomaterial catalysts for the sustainable production of 1,4-DHP derivatives.

Aristolochia species have been widely used in folk medicine. In this work, six solvent extracts of Aristoloia bodamae leaf, seed, and flower were investigated for the photochemical contents (TPC, TFC, and LC–MS/MS), bioactivities. Additionally, molecular docking was applied to identify whether the most abundant compounds in the extracts are responsible for the bioactivity. Total phenol and flavonoid content ranges were 10.32–160.54 mg GAE/g and 3.42–50.03 mg QE/g, respectively. The most common chemical found in most extracts was o-coumaric acid. Leaf extracts showed the highest total antioxidant, reducing power, and free radical removal activities. Seed extracts recorded the highest antibacterial activity, and for the inhibition activity seed extracts were also the highest in general. Molecular docking demonstrates firm binding between o-coumaric acid and AChE. The stability of the best-docked protein was evaluated using 100 ns molecular dynamic simulation and an MM-PBSA-assisted effective free energy estimation. The results showed that the interaction between this enzyme and the compound was remarkably stable according to energy and molecular dynamics calculations. Overall, aboveground extracts of A. bodamae exhibited high potential in reducing oxidative damage, enzyme inhibition, DNA protection potential, and antibacterial activities, probably due to their phenolic components and o-coumaric acid.

In this work, the biological activities of 29 novel quinazoline/phenylsulfonylfuroxan derivatives (1a–z, 1aa, 1ab, 2a, 2b, 2d, and 2f) were computationally investigated as potential anti-cancer inhibitors against five cell lines, i.e., H1975, MCF-7, Eca-109, MGC-803, and A549, which are involved in various diseases, including lung, breast, esophageal squamous carcinoma, and gastric cancer. The 2D-QSAR predictive approach, exploiting multiple linear regression (MLR) models and rigorous internal and external cross-validation, showed a correlation factor R² of range: 0.68−0.82. Moreover, the MLR-derived R²_test and Y randomization (R²_rand) values for the five cell lines are higher than 0.60 and less than 0.3, respectively, indicating a strong alignment with the internal and external validation data. New 70 quinazoline hybrids based on the most effective in vivo 1q inhibitor were designed, and their pIC₅₀ activity was predicted. The best-scoring 15 (N1–N15) compounds were further evaluated using molecular docking and dynamics simulations (100 ns) with the VEGFR-2 kinase target (PDB code: 3U6J). All the data sets accurately predict the strongest binding affinity for the selected (N6, N7, N9, and N11) molecules, as evidenced by the highest docking score, hydrogen bond energy, and significant amino acid steric interactions. Furthermore, the RMS/RMSF/R_g dynamics parameters show that the formed complexes are satisfactorily stable. The ADMET properties indicate that the selected new ligands have shown a promising drug-like profile and can be considered potential candidates for future anti-cancer therapies, with perspective validating their anticancer activity by in vitro and in vivo studies.

Thienopyridine derivatives are specifically designed for utilization in antithrombotic therapy to help combat cardiovascular disorders linked to thrombosis. This study introduces new thienopyridine derivatives with superior therapeutic efficacy through synergies by dual functional compounds, developed as antithrombotic agents. Through computational design, we discovered 32 compounds out of a library of 100 compounds that exhibit efficacy. The compounds are synthesized by multiple steps and subsequently purified using chromatographic procedures to achieve a purity level of >99%. Using the ADP-induced platelet aggregation assay, we have found 4 active test compounds (ACG-0173-19, ACG-0173-37, ACG-A-04, and ACG-B-03) out of a total of 32 compounds. On the other hand, ACG-0173-19, ACG-0173-37, ACG-A-04, and ACG-B-03 have demonstrated the highest percentage activity on factor Xa (FXa) inhibition. The ACG-A-04 chemical exhibited the highest hydrophilicity, specifically in terms of its aqueous solubility. It had a solubility of 0.44 mg/mL in pH 5.8, 0.29 mg/L in pH 6.2, and 0.145 mg/L in pH 7.4 buffers. In comparison, the standards APX-01 (apixaban) and PRG-01(prasugrel) had lower hydrophilicity. Based on cytotoxicity investigations, it was determined that the test substances do not exhibit harmful effects. The results indicated that the test chemicals can undergo hydrolysis in blood plasma rather than in other organs. Among the four test drugs, ACG-1073-19 exhibited an unbound fraction of 44.1%, which is twice as high as the standards (apixaban). ACG-1073-37 demonstrates superior plasma protein binding (33.2%) compared to all other test compounds. The compounds resulted in a higher expression of CD61, CD42b, and CD62P in platelets compared to the control. The ACG-1073-37 molecule had a Caco-2 permeability of 51%, which is extremely close to the Caco-2 permeability of the control medicines (55% for APX-01 and 62% for PRG-01). Through the assessment of microsomal stability, it was determined that ACG-1073-37 and ACG-A-04 exhibited metabolic stability for 42.4 and 34.14 min, respectively.

Glaucoma is one of the major causes of irreversible blindness worldwide. Increased intraocular pressure (IOP) is a key factor in the onset and progression of this disease. The drugs used to treat glaucoma influence a variety of biological targets. Azolopyrimidine derivatives have attracted significant attention as potential agents for the treatment of glaucoma because they presumed to be analogs of adenosine receptor (AR) agonists and antagonists. In this study, a series of novel 3(4)-alkyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-amines were synthesized to develop promising ophthalmic hypotensive drugs. The synthesized compounds demonstrated significant hypotensive activity against IOP, which opens new possibilities for glaucoma therapy.

Benzothiazinone analogs have emerged as a promising class of compounds having potent antimycobacterial activity, particularly against Mycobacterium tuberculosis, the pathogen responsible for tuberculosis. This review highlights the development of benzothiazinone analogs as potential antitubercular agents from the beginning to the recent advancement in the past decade. These compounds have shown potent activity, including drug-resistant strains of Mycobacterium tuberculosis. Structure–activity relationship studies and modifications have improved their efficacy. Benzothiazinone analogs have favorable pharmacokinetic profiles and show promise in preclinical studies. Challenges include addressing resistance mechanisms and ensuring safety. Their unique mode of action and promising properties make them attractive candidates for the battle against drug-resistant tuberculosis.

In this study, LiNaCO₃- and (Li-Na-K)₂CO₃-based porous carbon composites were synthesized from terephthalic acid, lithium hydroxide, sodium hydroxide, and potassium hydroxide at different calcination temperatures. These composite materials were characterized with X-Ray diffraction, scanning electron microscopy, and nitrogen adsorption and desorption. According to their CO₂ capture performance measured, LiNaC-700 °C had the largest CO₂ adsorption capacity of 66 mg CO₂ g⁻¹, while the CO₂ capture capacity of other materials doped with three metal ions was only up to 8.57 mg CO₂ g⁻¹. Additionally, the CO₂ adsorption capacity of each adsorbent was significantly higher than the N₂ adsorption capacity, showing their high CO₂ adsorption selectivity. Lithium-containing carbonate-based porous carbon materials (LiNaCO₃- and (Li-Na-K)₂CO₃-based porous carbon could effectively capture CO₂ with excellent reproducibility.