Expanding cyclodextrin use in normal phase and super/subcritical fluid chromatographic modes for the chiral separation of 1,4-dihydropyridines.

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-ß-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations.

Design, In silico Screening, Synthesis, Characterisation and DFT-based Electronic Properties of Dihydropyridine-based Molecule as L-type Calcium Channel Blocker.

BACKGROUND: People of all nationalities and social classes are now affected by the growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A range of therapeutic compounds, on the other hand, are often used to handle hypertension. OBJECTIVES: The objectives of this study are first to design potential antihypertensive drugs based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise the best ligand. MATERIALS AND METHODS: Due to the lack of 3D structures for human Cav1.2, the protein structure was modelled using a homology modelling approach. A protein-ligand complex's strength and binding interaction were investigated using molecular docking and molecular dynamics techniques. DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2- TZVP level of theory. The SwissADME website was used to study the ADMET properties. RESULTS: In this study, a series of DHP compounds (19 compounds) were properly designed to act as calcium channel blockers. Among these compounds, compound 16 showed excellent binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised. To assess the structural features of the synthesised molecule quantum chemical calculations were performed. CONCLUSION: Based on molecular docking, molecular dynamics simulations, and drug-likeness properties of compound 16 can be used as a potential calcium channel blocker.

Novel Far-Red Fluorescent 1,4-Dihydropyridines for L-Type Calcium Channel Imaging.

Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlock fast imaging protocols in live cells is coveted. Herein, we report a library of first-in-class far-red small-molecule-based fluorescent ligands (FluoDiPines), able to target LTCCs. All fluorescent ligands were evaluated in whole-cell patch-clamp and live-cell Ca2+ imaging whereby FluoDiPine 6 was found to be the best candidate for live-cell fluorescence imaging. Low concentration of FluoDiPine 6 (50 nM) and a quick labeling protocol (5 min) are successfully applied to fixed and live cells to image LTCCs with good specificity.

Design and synthesis of ferrocenyl 1,4-dihydropyridines and their evaluation as kinesin-5 inhibitors.

Kinesin-5 inhibitors offer cancer cell-targeted approach, thus securing reduced systemic toxicity compared to other antimitotic agents. By modifying the 1,4-dihydropyridine-based kinesin-5 inhibitor CPUYL064 with a ferrocenyl moiety (Fc), we designed and prepared a series of organometallic hybrids that show high antiproliferative activity, with the best compounds exhibiting up to 19-fold increased activity. This enhanced activity can be attributed to the presence of the ferrocenyl moiety.

1,4-Dihydropyridine-based FA1 site-specific fluorescent probes for the selective detection and quantification of HSA levels in biofluids.

Human serum albumin (HSA) is a multifunctional circulatory protein essential for many physiological processes including oncotic pressure maintenance, ligand/drug binding and transport, antioxidant activity, etc. Abnormal HSA levels in biological fluids have been reported in a variety of clinical disorders, making it a potential biomarker for early diagnosis. Low serum albumin levels have been linked to increased long- and short-term mortality rates in ICU patients. Therefore, quantifying HSA in biofluids such as serum and urine offers a convenient approach for the early identification of underlying clinical conditions and assessing the risk factors. Herein, we report a series of fluorescent 1,4-dihydropyridine (DHP) derivatives for the detection and quantification of HSA in biofluids. Their response towards HSA can be tuned by varying the substituents at the C-4 and the N-1 of the DHP ring. Depending on the nature of the substituents, they generated either a turn-on or ratiometric response with a LoD in low nanomolar or subnanomolar levels. A pair of enantiomers obtained by introducing a chiral center on the N-substituents highlighted the importance of stereochemistry in HSA-ligand interactions. Quantification of HSA in complex biofluids, such as blood serum and urine, was also accomplished using these probes. The high selectivity of some of the probes towards HSA over the homologous BSA allowed the discrimination of these two proteins. The preferred binding location of the probes was the hemin binding site and the detection mechanism was identified as the restriction of intramolecular rotation. Additionally, a prototype of a smartphone-integrated point-of-care device was also fabricated to demonstrate the feasibility of utilizing these probes in clinical settings.

Chiral superficially porous stationary phases for enantiomeric separation of condensed 1,4-dihydropyridine derivatives.

1,4-dihydropyridine (DHP) scaffold occupies a prominent position among all heterocyclic compounds owing to its versatile pharmacological properties, particularly its well-known calcium channel blocking activity. In the quest of developing new calcium channel blockers, fifty seven 5-oxo-hexahydroquinoline (HHQ) derivatives carrying DHP framework in a condensed ring system were recently synthesized as racemic mixtures. Due to their potential as drug candidates, enantiomers arising from the asymmetric center at the C-4 position of the HHQ ring were separated. Four modern columns packed with 2.7 µm superficially porous particles bonded with a chiral selector were used. The chiral selectors were three macrocyclic glycopeptide selectors: vancomycin, teicoplanin, and a macrocyclic derivative called nico. The fourth bonded selector was the dinitrobenzamido-tetrahydrophenanthrenyl derivative called Whelko. The four chromatographic modes were assayed with the mobile phase compositions: reversed phase with acetonitrile/buffer 30/70 %v/v, normal phase with hexane/ethanol 80/20 %v/v, and subcritical fluid chromatography with CO2/methanol 80/20 %v/v at 25 °C. The WhelkoShell column was the most effective in separating this set of 57 compounds. Several enantioresolution factors passed 20 with enantioselectivity ratios higher than 4. Molecular modeling showed that the compounds had a T-shape that fitted well the molecular structure of the WhelkoShell selector in the normal or subcritical modes. Additionally, seven compounds had a second chiral center. The NicoShell column was able to separate all four stereoisomers of these compounds in the reversed phase mode. The preparative production of pure enantiomers of these compounds would be straightforward using the WhelkoShell column in the subcritical mode.

Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment.

OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.

Establishing the Thermodynamic Cards of Dipine Models' Oxidative Metabolism on 21 Potential Elementary Steps.

Dipines are a type of important antihypertensive drug as L-calcium channel blockers, whose core skeleton is the 1,4-dihydropyridine structure. Since the dihydropyridine ring is a key structural factor for biological activity, the thermodynamics of the aromatization dihydropyridine ring is a significant feature parameter for understanding the mechanism and pathways of dipine metabolism in vivo. Herein, 4-substituted-phenyl-2,6-dimethyl-3,5-diethyl-formate-1,4-dihydropyridines are refined as the structurally closest dipine models to investigate the thermodynamic potential of dipine oxidative metabolism. In this work, the thermodynamic cards of dipine models' aromatization on 21 potential elementary steps in acetonitrile have been established. Based on the thermodynamic cards, the thermodynamic properties of dipine models and related intermediates acting as electrons, hydrides, hydrogen atoms, protons, and two hydrogen ions (atoms) donors are discussed. Moreover, the thermodynamic cards are applied to evaluate the redox properties, and judge or reveal the possible oxidative mechanism of dipine models.

Rational Design, Synthesis, and Computational Investigation of Dihydropyridine [2,3-d] Pyrimidines as Polyphenol Oxidase Inhibitors with Improved Potency.

Polyphenol oxidase (PPO) is an industrially important enzyme associated with browning reactions. In the present study, a set of ten new dihydropyridine [2,3-d] pyrimidines (TD-Hid-1-10) were synthesized and was found to be proven characteristically by 1H NMR, 13C NMR, IR, elemental analysis, and assessed as possible PPO inhibitors. PPO was purified from banana using three-phase partitioning, achieving an 18.65-fold purification and 136.47% activity recovery. Enzyme kinetics revealed that the compounds TD-Hid-6 and TD-Hid-7 are to be the most potent inhibitors, exhibiting mixed-type inhibition profile with IC50 values of 1.14 µM, 5.29 µM respectively against purified PPO enzyme. Electronic structure calculations at the B3LYP/PBE0 level of theories using def-2 SVP, def2-TZVP basis sets with various molecular descriptors characterized the electronic behavior of studied derivatives TD-Hid-1-10. Molecular electrostatic potential (MEP) and reduced density gradient analyses of RDG-NCI provided insights into charge distributions and weak intermolecular interactions. Docking study simulations predicted binding poses within crucial amino acid sequence in the 2y9x enzyme's active site, which is typically similar in sequence to the PPO form is not allowed. Ligands were analysed in terms of binding energies, inhibitor concentrations (mM) and various molecular interactions such as H-bonds, H-carbon, π-carbon, π-sigma, π-sigma, π-π T-shaped, π-π stacked, π-alkyl, Van der Waals and Cu interactions. The lowest binding energy (-7.83 kcal/mol) and the highest inhibitory effect (1.83 mM) were shown by the ligand Td-Hid-6, which forms H-bonds with Met280 and Asn260, exhibits π-sigma interactions with His61 and π-alkyl interactions with Val283. Other ligands also showed different interactions with various amino acids; for example, the Td-Hid-1 ligand formed H-bonds with His244 and showed π-sigma interactions with His244 and Val283.

Design, Synthesis, and Biological Evaluation of 1,4-Dihydropyridine-Indole as a Potential Antidiabetic Agent via GLUT4 Translocation Stimulation.

In the quest for the discovery of antidiabetic compounds, a series of 27 1,4-dihydropyridine-indole derivatives were synthesized using a diversity approach. These compounds were systematically evaluated for their antidiabetic activity, starting with an in vitro assessment for GLUT4 translocation stimulation in L6-GLUT4myc myotubes, followed by in vivo antihyperglycemic activity evaluation in a streptozotocin (STZ)-induced diabetic rat model. Among the synthesized compounds, 12, 14, 15, 16, 19, 27, and 35 demonstrated significant potential to stimulate GLUT4 translocation in skeletal muscle cells. Compound 19 exhibited the highest potency and was selected for in vivo evaluation. A notable reduction of 21.6% (p < 0.01) in blood glucose levels was observed after 5 h of treatment with compound 19 in STZ-induced diabetic rats. Furthermore, pharmacokinetic studies affirmed that compound 19 was favorable to oral exposure with suitable pharmacological parameters. Overall, compound 19 emerged as a promising lead compound for further structural modification and optimization.

Optimization of diastereomeric dihydropyridines as antimalarials.

The increase in research funding for the development of antimalarials since 2000 has led to a surge of new chemotypes with potent antimalarial activity. High-throughput screens have delivered several thousand new active compounds in several hundred series, including the 4,7-diphenyl-1,4,5,6,7,8-hexahydroquinolines, hereafter termed dihydropyridines (DHPs). We optimized the DHPs for antimalarial activity. Structure-activity relationship studies focusing on the 2-, 3-, 4-, 6-, and 7-positions of the DHP core led to the identification of compounds potent (EC50 < 10 nM) against all strains of P. falciparum tested, including the drug-resistant parasite strains K1, W2, and TM90-C2B. Evaluation of efficacy of several compounds in vivo identified two compounds that reduced parasitemia by >75 % in mice 6 days post-exposure following a single 50 mg/kg oral dose. Resistance acquisition experiments with a selected dihydropyridine led to the identification of a single mutation conveying resistance in the gene encoding for Plasmodium falciparum multi-drug resistance protein 1 (PfMDR1). The same dihydropyridine possessed transmission blocking activity. The DHPs have the potential for the development of novel antimalarial drug candidates.

18F-Labeled dihydropyridines via Hantzsch reaction for positron emission tomography of P-glycoprotein dysfunction.

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.

Photostability evaluation of manidipine tablets and structural determination of its photoproducts.

Manidipine (MP) is a dihydropyridine drug, which is treated for the reduction of high blood pressure. The aim of this study is to clarify the photochemical behavior of MP in the case of ultraviolet light (UV) irradiation for MP tablets (Calslot® tablets). The tablets and its altered forms (powders and suspensions) were UV-irradiated using a black light, and residual amounts of active pharmaceutical ingredients (APIs) were monitored by high-performance liquid chromatography (HPLC). Due to the photoproducts of MP were detected in HPLC chromatograms, the elucidation of their chemical structures was carried out utilizing electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). As a result, APIs in Calslot® tablets were almost completely photodegraded in the case that Calslot® tablets were suspended in an aqueous media along with the generation of some MP photoproducts. LC-ESI-MS/MS analysis clarified the chemical structures of three MP photoproducts, indicating that they were a pyridine analogue, benzophenone and a hydrolysate. Benzophenone was a main MP photoproduct. It was possible that MP might be firstly oxidized to form its pyridine analogue, followed by the oxidation of a dimethyl methylene moiety. This moiety seemed to be eliminated as a benzophenone, and the cleavage of an ester bond of the residual moiety resulted in the generation of a hydrolysate. Finally, toxicological potencies of MP and its photoproducts were predicted in silico toxicity evaluation, suggesting some of biological effects of the photoproducts might be altered compared with MP.

Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 µg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Positron Emission Tomography of Nitric Oxide by a Specific Radical-Generating Dihydropyridine Tracer.

Nitric oxide (NO) plays a pivotal role as a biological signaling molecule, presenting challenges in its specific detection and differentiation from other reactive nitrogen and oxygen species within living organisms. Herein, a 18F-labeled (fluorine-18, t1/2 = 109.7 min) small-molecule tracer dimethyl 4-(4-(4-[18F]fluorobutoxy)benzyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ([18F]BDHP) is developed based on the dihydropyridine scaffold for positron emission tomography (PET) imaging of NO in vivo. [18F]BDHP exhibits a highly sensitive and efficient C-C cleavage reaction specifically triggered by NO under physiological conditions, leading to the production of a 18F-labeled radical that is readily retained within the cells. High uptakes of [18F]BDHP are found within and around NO-generating cells, such as macrophages treated with lipopolysaccharide or benzo(a)pyrene. MicroPET/CT imaging of arthritic animal model mice reveals distinct tracer accumulation in the arthritic legs, showcasing a higher distribution of NO compared with the control legs. In summary, a specific radical-generating dihydropyridine tracer with a unique radical retention strategy has been established for the marking of NO in real-time in vivo.

Evaluation of Novel Benzo-annelated 1,4-dihydropyridines as MDR Modulators in Cancer Cells.

BACKGROUND: Multidrug resistance (MDR) is the main problem in anticancer therapy today. Causative transmembrane efflux pumps in cancer cells have been reconsidered as promising anticancer target structures to restore anticancer drug sensitivity by various strategies, including MDR modulators. MDR modulators interfere with the efflux pumps and improve the cellular efficiency of chemotherapeutics. So far, only a few candidates have gone through clinical trials with disappointing results because of low specificity and toxic properties. AIM: This study aimed to find novel MDR modulators to effectively combat multidrug resistance in cancer cells. OBJECTIVE: We synthesized various novel benzo-annelated 1,4-dihydropyridines to evaluate them as MDR modulators towards ABCB1 in cancer cells. METHODS: Synthesized compounds were purified by column chromatography. The MDR modulation of ABCB1 was determined in cellular efflux assays using the flow cytometry technique and cellular fluorescent measurements by the use of each fluorescent substrate. RESULTS: Compounds were yielded in a two-step reaction with structurally varied components. Further, substituent- dependent effects on the determined MDR inhibiting properties towards ABCB1 were discussed. Cellular studies prove that there is no toxicity and restoration of cancer cell sensitivity towards the used anticancer drug. CONCLUSION: Novel MDR modulators could be identified with favorable methoxy and ester group functions. Their use in both ABCB1 non-expressing and overexpressing cells proves a selective toxicity-increasing effect of the applied anticancer agent in the ABCB1 overexpressing cells, whereas the toxicity effect of the anticancer drug was almost unchanged in the non-expressing cells. These results qualify our novel compounds as perspective anticancer drugs compared to MDR modulators with nonselective toxicity properties.

Sensitive and effective method with 96-well plate for determination of levamlodipine in human plasma using LC-MS/MS.

we developed an effective protein precipitation method for determination of levamlodipine in human plasma using LC-MS/MS. Sample extraction was carried out by using liquid-liquid extraction in 96-well plate format. (S)-Amlodipine-d4 was used as internal standard (IS). The chromatographic separation was achieved using Philomen Chiral MX (2) column (3 µm, 2.1 × 100 mm). Mobile phase A was comprised of Acetonitrile (ACN), Mono ethanol amine (MEA) and Iso-Propyl alcohol (IPA) (1000:1:10, v/v/v), Mobile phase B was IPA-ACN (2:1, v/v). The flow rate was 0.4 mL/min. The total run time of each sample was 4.0 min with gradient elution. LC-MS/MS spectra were generated in positive ion mode, and multiple reaction monitoring (MRM) was used to detect the following transitions: m/z 409.20 â†’ 238.15 for levamlodipine and 415.25 â†’ 240.20 for (S)-Amlodipine-d4 (the IS). The method was linear from 50 to 10000 pg/mL（R2＝0.9988489）,and the lower limit of quantification (LLOQ) was 50 pg/mL. This method was applied to a bioequivalence study of levamlodipine.

Discovery of Novel Aryl Triazolone Dihydropyridines (ATDPs) Targeting Highly Conserved Residue W229 as Promising HIV-1 NNRTIs.

NNRTI is an important component of the highly active antiretroviral therapy (HAART), but the rapid emergence of drug resistance and poor pharmacokinetics limited their clinical application. Herein, a series of novel aryl triazolone dihydropyridines (ATDPs) were designed by structure-guided design with the aim of improving drug resistance profiles and pharmacokinetic profiles. Compound 10n (EC50 = 0.009-17.7 µM) exhibited the most active potency, being superior to or comparable to that of doravirine (DOR) against the whole tested viral panel. Molecular docking was performed to clarify the reason for its higher resistance profiles. Moreover, 10n demonstrated excellent pharmacokinetic profile (T1/2 = 5.09 h, F = 108.96%) compared that of DOR (T1/2 = 4.4 h, F = 57%). Additionally, 10n was also verified to have no in vivo acute or subacute toxicity (LD50 > 2000 mg/kg), suggesting that 10n is worth further investigation as a novel oral NNRTIs for HIV-1 therapy.

A Highly Chemically Robust 3D Interpenetrated MOF Heterogeneous Catalyst for the Synthesis of Hantzsch 1,4-Dihydropyridines and Drug Molecules.

Metal-organic frameworks (MOFs) have attracted immense attention as efficient heterogeneous catalysts over other solid catalysts, however, their chemical environment instability often limits their catalytic potential. Herein, utilizing a flexible unexplored tetra-acid ligand and employing the mixed ligand approach, a 3D interpenetrated robust framework is strategically developed, IITKGP-51 (IITKGP stands for Indian Institute of Technology Kharagpur), which retained its crystallinity over a wide range of pH solution (4-12). Having ample open metal sites (OMSs), IITKGP-51 is explored as a heterogeneous catalyst in one-pot Hantzsch condensation reaction, with low catalyst loading for a broad range of substrates. The synthesis of drug molecules remains one of the most significant and emergent areas of organic and medicinal chemistry. Considering such practical utility, biologically important Nemadipine B and Nifedipine drug molecules (calcium channel protein inhibitor) are synthesized for the first time by using this catalyst and fully characterized via SC-XRD and other spectroscopic methods. This report inaugurates the usage of a MOF material as a catalyst for the synthesis of drug molecules.

Synthesis, Anticancer Evaluation and in Silico Studies of 1,4-Dihydropyridines.

An efficient 1,4-dihydropyridine synthesis under mild conditions has been developed. Numerous substrates were tested, with yields of 1,4-dihydropridines ranging from good to excellent and a wide range of functional group tolerance. A549, HT-29, and HepG2 cancer cells were used to investigate the anticancer efficacy of each of the produced compounds. Additionally, in-silico docking studies were conducted to understand the structure-based features of the anticancer mechanism with the cancer medication target of Adenosine A2A receptor as well as the molecular level interactions of the compounds.