Search Results (214)

Background/Objectives: This study investigates the pharmacological potential of 1,4-dihydropyridine derivatives, functionalized with an imidazo[2,1-b]thiazole scaffold, as selective modulators of intestinal motility. Given their structural similarity to both L-type calcium channel blockers and spasmolytics such as Otilonium Bromide (OB), we explored their repurposing for the treatment of gut motility disorders. Methods: A focused library of 83 1,4-dihydropyridine derivatives was screened for spasmolytic activity on potassium (80 mM)-induced depolarization in isolated guinea pig ileal and colonic tissues. Compounds showing pharmacodynamic profiles similar to OB and nifedipine were further evaluated for their effects on the spontaneous contractility of longitudinal and circular smooth muscle layers. Additional functional assays assessed intestinal transit, visceral nociception, and mixing/fragmentation efficiency. Microbiota safety was preliminarily tested on mixed cultures of Bifidobacterium and Lactobacillus species. Results: Compounds 62 and 65 selectively relaxed intestinal smooth muscle, primarily targeting the longitudinal layer without affecting vascular contractility. Ex vivo testing highlights that compounds 62 and 65 could both modulate gut transit and mixing without causing functional constipation or pain. Microbiota analyses showed no detrimental effects on “good” bacterial species Bifidobacterium and Lactobacillus spp. Conclusions: The favorable gastrointestinal and microbiological profiles of compounds 62 and 65, combined with their structural versatility, support their potential repurposing for functional bowel disorders. Their selective activity suggests a promising role in therapies targeting intestinal motility while preserving microbiota homeostasis, supporting the need for extended pharmacological characterization. Full article

A novel general approach to cyclic hydrazide–hydrazone compounds with a dihydropyridine-2-one core has been developed, involving annulation of symmetrical aldazines with 3-arylglutaconic anhydrides. This approach provides the benefits of straightforward and catalyst-free procedures, diastereoselectivity, and the ability to switch between two isomeric dihydropyridine-2-one cores based on the reaction temperature. Several post-modifications were performed on the side functional groups and the core to demonstrate the synthetic potential of the resulting products. This approach significantly expands the chemical diversity of medicinally relevant N-functionalized δ-lactams. Full article

Background: This study aimed to evaluate the risk of upper gastrointestinal (UGI) adverse events (AEs) associated with oral anticoagulants (OACs) and identify potential interactions with cardiovascular (CV) drugs. Methods: Individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System from July 2014 to December 2023 were analyzed. Dataset I was constructed to assess the associations between OACs and UGI AEs using disproportionality analysis. Dataset Ⅱ included OAC-related ICSRs to explore potential interactions with CV drugs through logistic regression. Positive signals were defined as potential associations identified by disproportionality analysis metrics, such as reporting odds ratios (RORs) or adjusted RORs (aRORs) accounting for confounders. Results: Dataset I included 12,905,290 ICSRs, and a positive signal for dabigatran was detected with an ROR of 1.19 (95% CI, 1.13–1.25). A total of 364,044 OAC-related ICSRs were included in dataset II. At the pharmacologic drug class level, several positive signals were identified, represented as aRORs with 95% CIs: for warfarin, amiodarone analogs (1.22; 1.04–1.43); for apixaban, angiotensin-converting enzyme inhibitors (1.34; 1.24–1.45), angiotensin receptor blockers (1.23; 1.14–1.33), dihydropyridine calcium channel blockers (1.30; 1.21–1.41), and digitalis glycosides (1.72; 1.49–2.00); and for edoxaban, angiotensin receptor blockers (1.88; 1.48–2.37), amiodarone analogs (1.73; 1.06–2.85), and anti-platelets (1.56; 1.20–2.03). No signals were observed for rivaroxaban or dabigatran. At the individual drug level, 62 OAC-CV pairs were identified as having potential interactions. Conclusions: Drug-specific interaction profiles should be considered to ensure safe and personalized use of OACs in clinical practice. Full article

Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article

Multicomponent reactions (MCRs) enable the efficient assembly of complex small molecules via multiple bond-forming events in a single step. However, individual MCRs typically yield products with similar core structures, limiting access to larger, more intricate scaffolds. Strategic selection of reactants allows the combination of distinct MCRs, thus facilitating the synthesis of advanced molecular architectures with potential biological significance. Using our previously reported method for performing the aza-Friedel Crafts multicomponent reaction under green heterogeneous conditions, we have incorporated some of the obtained products into diverse multicomponent reactions to generate, in an unprecedent approach, eight novel products, some of which were also characterized by two-dimensional NMR techniques. The biological properties of such products are under investigation. Full article

The intermediate compound 4′-phenyl-1′,4′-dihydro-2,2′:6′,2″-terpyridine (pdhtpy) was isolated for the first time during the synthesis of 4′-phenyl-2,2′:6′,2″-terpyridine (ptpy) and characterised by single-crystal X-ray diffraction. Pdhtpy crystallises in the triclinic crystal system with space group P$\bar{1}$ with the following unit cell parameters at 100 K: a = 6.1325(4) Å; b = 8.2667(5) Å; c = 16.052(2) Å; α = 86.829(2)°; β = 82.507(2)°; γ = 84.603(2)°; V = 802.49(9) ų. The absence of stabilising electron-withdrawing groups renders pdhtpy prone to oxidative conditions. Pdhtpy was obtained as a mixture with ptpy, confirmed by Rietveld refinement of the powder X-ray diffraction pattern. Notably, pdhtpy is the first solid-state 1,4-dihydropyridine lacking electron-withdrawing groups at both positions 3 and 5, distinguishing it from Hantzsch esters and related compounds. Full article

This work studies the effect of mesostructured silica–zirconia–tungstophosphoric acid (SiO₂-ZrO₂-TPA) composites used as catalysts in the synthesis of nifedipine by the Hantzsch methodology. The selectivity for nifedipine is determined, along with that of secondary products that may form depending on the reaction conditions. The materials were synthesized via the sol–gel method and characterized by N₂ adsorption–desorption isotherms, infrared spectroscopy (FT-IR), ³¹P solid-state nuclear magnetic resonance (NMR-MAS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), X-ray photoelectron spectra (XPS), and potentiometric titration. The characterization results from the XPS spectra showed that as the Si/Zr ratio drops, the Si-O-Si signal size decreases, while the Zr-O signal size increases. Characterization by titration indicated that an increase in the total acidity of the material, resulting from support modification with tungstophosphoric acid (H₃PW₁₂O₄₀, TPA), enhances the reaction yield. The catalytic activity in the solvent-free Hantzsch reaction was evaluated under thermal heating and microwave irradiation. The experiments conducted at 80 °C achieved a maximum yield of 57% after 4 h of reaction using the Si20Zr80TPA30 catalyst (50 mg), while by microwave heating, the yield significantly improved, reaching 77% in only 1 h of reaction. This catalyst exhibited stability and reusability without significant loss of activity up to the third cycle. Depending on the type of material and the reaction conditions, it is possible to modify the selectivity of the reaction, obtaining a 1,2-dihydropyridine isomeric to nifedipine. Reaction intermediates and other minor secondary products that may be formed in the process were also evaluated. Full article

Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article

Background/Objectives: Lercanidipine is a third-generation dihydropyridine calcium channel blocker. In addition to their well-established cardiovascular effects, calcium channel blockers are increasingly recognized for their therapeutic potential in various cancers. This study aimed to investigate the potential anticancer effects of lercanidipine on cancer cell lines—particularly in combination with cisplatin—by assessing parameters such as cell viability (MTT assay), proliferation, MAPK pathway activity, caspase enzyme levels, and TNF-α expression. Methods: In this study, the effects of lercanidipine, both alone and in combination with cisplatin, on cell viability were evaluated using the MTT assay in MCF-7, SH-SY5Y, PC3, and HEK293 cell lines. To assess intracellular signaling and apoptotic pathways, MAPK inhibition, as well as caspase-3 and caspase-8 activities, were measured using ELISA. Additionally, to evaluate the anti-inflammatory potential, TNF-α levels in LPS-stimulated RAW264.7 cells were analyzed via. Results: The study revealed that lercanidipine showed significant cytotoxic effects, particularly in SH-SY5Y and PC3 cancer cell lines, while it did not induce a 50% loss of viability in healthy HEK293 cells. When combined with cisplatin, lercanidipine enhanced cytotoxicity by 2.7-fold in neuroblastoma (SH-SY5Y) cells, 1.6-fold in breast cancer (MCF7) cells, and 1.9-fold in prostate cancer (PC3) cells. MAPK activity was inhibited by 83.6% at 20 μM lercanidipine, while dose-dependent increases in caspase-3 and caspase-8 activities were observed. Additionally, lercanidipine decreased TNF-α levels in LPS-stimulated RAW264.7 cells, indicating its potential anti-inflammatory effect. Conclusions: In conclusion, lercanidipine demonstrated selective anticancer effects in cancer cell lines and showed synergistic cytotoxicity when combined with cisplatin. It also significantly inhibited MAPK signaling, activated apoptotic caspases, and reduced TNF-α levels, suggesting potential anti-inflammatory activity. These findings highlight lercanidipine’s potential for repurposing as an adjunct in cancer therapy. Full article

The growing threat of bacterial resistance, coupled with the increasing costs associated with drug development, poses significant challenges in the discovery of new antibiotics. The present study reports the synthesis and antimicrobial evaluation of 1,4-dihydropyridine (1,4-DHP) derivatives derived from chalcones, using silica-mediated magnetic iron oxide, Fe₂O₃@SiO₂ nanoparticles as a nanocatalyst. The nanoparticles were characterized using FT-IR, SEM-EDS, XRD, Zeta-Potential, and VSM techniques to confirm their structure and properties. Among them, the series 8a–e (particularly compound 8c) demonstrated strong antimicrobial activity, with effectiveness comparable to standard drugs Fluconazole and Amoxicillin; this was attributed to the presence of polar groups. Other derivatives exhibited moderate activity, with MICs ranging from 25 to 50 μg/mL, while no significant activity was observed against Gram-negative bacteria. These compounds hold potential as promising antimicrobial agents and warrant further investigation for the development of effective therapies. Full article

Iodine is one of the key elements that must be removed from the off-gas systems of nuclear fuel reprocessing. This study systematically investigates the iodine vapor adsorption performance of the metal–organic framework (MOF) material HKUST-1(1-(2-methyl-4-(2-oxopyrrolidin-1-yl)phenyl)-3-morpholino-5,6-dihydropyridin-2(1H)-one), with particle sizes of 100 nm and 20 μm. HKUST-1 samples with varying particle sizes were synthesized via a hydrothermal method. The experimental results show that the 20 μm HKUST-1 exhibits superior crystallinity, a more intact pore structure, and a higher iodine adsorption capacity, reaching 700 mg/g, which is significantly greater than the 300 mg/g capacity of the 100 nm HKUST-1. Kinetic analysis reveals that the adsorption process follows the pseudo-second-order model, with physical adsorption as the predominant mechanism, where iodine molecules are accommodated within the pores. FTIR and XRD further confirm the structural stability of the HKUST-1 framework after iodine adsorption. However, desorption experiments show that iodine molecules are easily volatilized into the air, with a 20% weight loss observed within 10 h and a color change from black to green. The results provide experimental evidence for optimizing the application of HKUST-1 materials in iodine capture and suggest that material modification could enhance the long-term stability of iodine fixation. Full article

Here, we present a photothermally triggered drug delivery nanosystem MoS₂-NIMO-CHIT-SH, using the thiolated chitosan (CHIT-SH)-modified molybdenum disulfide (MoS₂) nanosheets as near-infrared (NIR) photo-responsive carriers, loaded with the dihydropyridine calcium antagonist drug Nimodipine (NIMO). Although NIMO is used to treat stroke, migraine, Alzheimer’s disease, cerebrovascular spasms, and hypertension, this drug is poorly water-soluble, with low bioavailability and lack of selectivity. Thus, there is an urgent need for a novel approach to creating NIMO formulations that are safe, effective, and have better solubility and bioavailability. To overcome these problems, we develop a cationic biopolymer functionalized MoS₂ nanosheets as a photothermal drug carrier system to facilitate the NIR light-induced release of NIMO drugs. MoS₂ nanosheets (<150 nm) as NIMO drug carriers are prepared through simple exfoliation of their bulk phase and then functionalized with CHIT-SH biopolymer to increase their physiological stability and biocompatibility. According to the results, MoS₂-NIMO-CHIT-SH nanocomposites show strong NIR absorbance, which makes them a promising candidate for photothermal therapy. Full article

The use of nicotinamide cofactors in cell-free biocatalytic systems is necessitated by the high specificity that these enzymes show for their natural redox mediators. Unfortunately, isolation and use of natural cofactors is costly, which suggests that enhancing their stability is key to enabling their use in industrial processes. This study details NAD⁺ and NADH stability in three buffer systems (sodium phosphate, HEPES, and Tris) at 19 °C and 25 °C and for up to 43 d. In Tris, both NADH and NAD⁺ were found to be highly stable. NADH degradation rates of 4 μM/d (19 °C) and 11 μM/d (25 °C) were observed in Tris buffer, corresponding to >90% and 75% remaining after 43 d, respectively. Higher degradation rates (up to 34 μM/d) were observed when sodium phosphate or HEPES buffers were used. The effect of a mild increase in temperature was determined to be significant for long-term stability, and it was shown that degradation under these conditions can be easily monitored via UV–Vis, because the degradation proceeds via the oxidation/de-aromatization of the dihydropyridine ring. Overall, this work emphasizes that the choice of buffer system is consequential for bioreactor systems employing natural nicotinamide cofactors for extended periods of time. Full article

Selenium compounds have garnered significant attention in the field of medicinal chemistry due to their unique biochemical properties and potential therapeutic applications for different pathologies. In this study, we report the synthesis of a new selenylated bis-pyridone compound using SeO₂ as the source of selenium. Detailed ¹H and ¹³C NMR characterizations and mass spectral analysis are given. Full article

A method for the synthesis of C4-benzhydryl-functionalized 3,4-dihydropyridin-2-ones using complementary addition of benzhydryllithium and/or benzhydrylmagnesiate reagents to 2-pyridones, with high regioselectivity triggered by substituents, is described. A partially stereoselective cyclization was successfully demonstrated using TfOH and/or TIPSOTf as Brønsted and Lewis acids, respectively, leading to C6-phenyl-functionalized 7,8-benzomorphanones. It is also shown that the use of functionalized δ-enelactams obtained with an active methoxy-substituted benzyl group at C3 enabled the preparation of a new C3–C6 bridged system within the δ-lactam framework. Full article