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Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies

In the present study, we designed three novel compounds via the combination of two precious nitrogencontaining scaffolds; 1,4-dihydropyridine (DHP) and azole, in the same molecule. To synthesize the title compounds, initially, azolyl benzaldehydes were obtained through the nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with pyrazole, imidazole or 1,2,4-triazole. Subsequently, an unsymmetrical Hantzsch reaction was applied to achieve DHP scaffold, thus the target molecules. After structural characterization, the effects of various azole rings on optical and non-linear optical (NLO) properties were investigated by computational methods. Band gaps, chemical hardness/softness, dipole moments, average polarizability, first hyperpolarizability values were computed for the target compounds at the CAM-B3LYP/6-31++G(d,p) level of theory. The comparable results confirmed the potential of DHP-azole hybrids to be utilized in NLO devices. The title molecules were further tested for their antibacterial and antifungal activities following the evaluation of their drug likeness properties. The compounds containing imidazole or triazole rings represented better antifungal properties than antibacterial activities. Molecular docking studies were performed in the catalytic site of lanosterol 14 alpha-demethylase, CYP51, from Candida albicans to explain the obtained biological results and suggest molecular modifications to endow this class of molecules with improved antifungal effects

Synthesis, structural characterization and myorelaxant activity of 4-naphthylhexahydroquinoline derivatives containing different ester groups

Gunduz, Miyase Gozde/0000-0002-2287-9509; Bayram, Cem/0000-0001-8717-4668; SARIOGLU, YUSUF/0000-0002-9227-365XWOS: 000382175400001The present study reports the synthesis, structural characterization and myorelaxant activity evaluation of a series of 16 novel 4-naphthylhexahydroquinoline derivatives. The compounds were achieved by one-pot microwave-assisted method via a modified Hantzsch reaction. The structures of the compounds were confirmed by various spectral methods, such as IR, 1D and 2D NMR techniques and mass analysis. X-Ray studies of compound 10 provided further evidence for the proposed structure. To evaluate their myorelaxant activities, the E-max and pD(2) values of the compounds and nifedipine were determined on isolated rabbit gastric fundus smooth muscle strips. The obtained results indicated that the introduction of long chain alkyl groups, such as the 2-methoxyethyl or 2-(methacryloyloxy)ethyl moiety, to the ester group led to the most active compounds.Scientific Research Fund of Hacettepe University, TurkeyHacettepe University [013.D03.301.001]; NSF-MRI programNational Science Foundation (NSF)NSF - Office of the Director (OD) [CHE-0619278]The authors gratefully acknowledge the financial support provided by the Scientific Research Fund of Hacettepe University, Turkey through Project 013.D03.301.001.; RJB wishes to acknowledge the NSF-MRI program (grant CHE-0619278) for funds to purchase the diffractometer and the Howard University Nanoscience Facility for access to liquid nitrogen

Structure-Activity Relationships Of Receptor Binding Of 1,4-Dihydropyridine Derivatives

The present study was undertaken to investigate binding activity of synthesized 1,4-dihydropyridine (1,4-DHP) derivatives (Compounds 1-124) to 1,4-DHP calcium channel antagonist receptors in rat brain. Sixteen 1,4-DHP derivatives inhibited specific (+)-[H-3]PN 200-110 binding in rat brain in a concentration-dependent manner with IC50 value of 0.43 to 3.49 mu M. Scatchard analysis revealed that compounds 54, 69, 85, like nifedipine, caused a significant increase in apparent dissociation constant (K-d) for (+)-[H-3]PN 200-110, while compounds 68, 69 and 80 caused a significant decrease in maximal number of bindings sites (B-max). These data suggest that compounds 68, 69 and 80 exert longer-acting antagonistic effects of 1,4-DHP receptors than compounds 54, 69 and 85. The structure-activity relationship study has revealed that 1) ester groups in 3- and 5-positions are the most effective, 2) the aryl group in the 4-position of 1,4-DHP ring is the basic requirement for optimal activity, 3) position and type of electron-withdrawing groups on phenyl group at position 4 would affect the receptor-binding activity. Furthermore, compound 58 exerted alpha 1 receptor binding activity, being 1.6 times greater than 1,4-DHP receptors. Compounds 81, 84, 91, 94, 106, 108 and 109 showed significant binding of ATP-sensitive potassium (K-ATP) channel, and the binding activities of compounds 81, 84, 108 and 109 were 1.6-3.8 times greater than the binding activity for 1,4-DHP receptors. Compounds 91 and 106 had similar binding activity for K-ATP channel and 1,4-DHP receptors. In conclusion, the present study has shown that novel 1,4-DHP derivatives exert relatively high binding affinity to 1,4-DHP receptors and has revealed new aspect of structure-activity relationships of 1,4-DHP derivatives, especially hexahydroquinoline derivatives.WoSScopu

Microwave-Assisted Synthesis Of Condensed 1,4-Dihydropyridines As Potential Calcium Channel Modulators

This study reports the design, synthesis, and calcium channel modulatory activity evaluation of a series of 14 novel fused 1,4-dihydropyridine derivatives. The molecular design of the compounds was based on modifications of nifedipine, which is a calcium channel blocker. The compounds were achieved by one-pot microwave-assisted reaction of 4,4-dimethyl-1,3-cyclohexanedione, 5-chlorosalicylaldehyde/3,5-dichlorosalicylaldehyde, an appropriate alkyl acetoacetate, and ammonium acetate in ethanol according to a modified Hantzsch reaction. The structures of the compounds were confirmed by spectral methods and elemental analysis. To evaluate their relaxant activities, the maximum relaxant response (E-max) and pD(2) values of the compounds and nifedipine were determined on isolated rat aorta rings. The obtained results indicated that all compounds produced concentration-dependent relaxation on the rings possibly due to the blockade of calcium channels. The E-max values (a measure of efficacy) of five compounds were higher than those of nifedipine.WoSScopu

Synthesis, structural characterization and myorelaxant activity of 4-naphthylhexahydroquinoline derivatives containing different ester groups

The present study reports the synthesis, structural characterization and myorelaxant activity evaluation of a series of 16 novel 4-naphthylhexahydroquinoline derivatives. The compounds were achieved by one-pot microwave-assisted method via a modified Hantzsch reaction. The structures of the compounds were confirmed by various spectral methods, such as IR, 1D and 2D NMR techniques and mass analysis. X-Ray studies of compound 10 provided further evidence for the proposed structure. To evaluate their myorelaxant activities, the E-max and pD(2) values of the compounds and nifedipine were determined on isolated rabbit gastric fundus smooth muscle strips. The obtained results indicated that the introduction of long chain alkyl groups, such as the 2-methoxyethyl or 2-(methacryloyloxy)ethyl moiety, to the ester group led to the most active compounds