Search Results (7)

Molecular interactions of 4-diphenylmethoxy-1-methylpiperidine derivatives with the calcium channel CaV1.1 (pdb:6JP5) are described. All the compounds tested, previously shown to inhibit adrenergic vascular contractions, display similar binding energetics and interactions with the trans-membrane domain of 6JP5 on the opposite side relative to the channel pore, where nifedipine, a known dihydropyridine Ca²⁺ channel blocker binds. Additionally, the compounds tested inhibit Ca²⁺-dependent contractions in isolated mouse mesenteric arteries. Thus, diphenylpyraline analogs may exert their anticontractile effects, at least partially, by blocking vascular Ca²⁺ channels. Full article

The necessity for the discovery of innovative antimicrobials to treat life-threatening diseases has increased as multidrug-resistant bacteria has spread. Due to antibiotics’ availability over the counter in many nations, antibiotic resistance is linked to overuse, abuse, and misuse of these drugs. The World Health Organization (WHO) recognized 12 families of bacteria that present the greatest harm to human health, where options of antibiotic therapy are extremely limited. Therefore, this paper reviews possible new ways for the development of novel classes of antibiotics for which there is no pre-existing resistance in human bacterial pathogens. By utilizing research and technology such as nanotechnology and computational methods (such as in silico and Fragment-based drug design (FBDD)), there has been an improvement in antimicrobial actions and selectivity with target sites. Moreover, there are antibiotic alternatives, such as antimicrobial peptides, essential oils, anti-Quorum sensing agents, darobactins, vitamin B6, bacteriophages, odilorhabdins, 18β-glycyrrhetinic acid, and cannabinoids. Additionally, drug repurposing (such as with ticagrelor, mitomycin C, auranofin, pentamidine, and zidovudine) and synthesis of novel antibacterial agents (including lactones, piperidinol, sugar-based bactericides, isoxazole, carbazole, pyrimidine, and pyrazole derivatives) represent novel approaches to treating infectious diseases. Nonetheless, prodrugs (e.g., siderophores) have recently shown to be an excellent platform to design a new generation of antimicrobial agents with better efficacy against multidrug-resistant bacteria. Ultimately, to combat resistant bacteria and to stop the spread of resistant illnesses, regulations and public education regarding the use of antibiotics in hospitals and the agricultural sector should be combined with research and technological advancements. Full article

4’4 bromophenyl 4’piperidinol derivatives were synthesized, and evaluated as multifactorial agents for the treatment of Alzheimer’s disease (AD). Among all the analogues, AB11 and AB14 showed the best activity against acetylcholinesterase (AChE) with IC₅₀ = 0.029 μM and 0.038 μM, respectively. Both compounds also acted as a good antioxidant agent (IC₅₀ = 26.38 μM for AB11 and 23.99 μM for AB14), while AB11 is the only molecule that displayed moderate inhibition of amyloid beta (Aβ) (43.25% at 500 μM). AB11 and AB14 were found selective against monoamine oxidase-B (MAO-B) with IC₅₀ values of 866 μM and 763 μM, respectively. AB10, AB17, and AB70 exhibited activity against both MAO-A and MAO-B and showed inhibitory potential against acetylcholinesterase; moreover, all analogues are capable of disassembling the well-structured Aβ fibril. Molecular modeling of selected compounds displayed interactions with the active site of human MAO-B and AChE enzyme. The results suggested that AB11 is a promising multi-target hit that can be optimized further as a successful drug molecule for the treatment of AD. Full article

Novel drugs to treat tuberculosis are required and the identification of potential targets is important. Piperidinols have been identified as potential antimycobacterial agents (MIC < 5 μg/mL), which also inhibit mycobacterial arylamine N-acetyltransferase (NAT), an enzyme essential for mycobacterial survival inside macrophages. The NAT inhibition involves a prodrug-like mechanism in which activation leads to the formation of bioactive phenyl vinyl ketone (PVK). The PVK fragment selectively forms an adduct with the cysteine residue in the active site. Time dependent inhibition of the NAT enzyme from Mycobacterium marinum (M. marinum) demonstrates a covalent binding mechanism for all inhibitory piperidinol analogues. The structure activity relationship highlights the importance of halide substitution on the piperidinol benzene ring. The structures of the NAT enzymes from M. marinum and M. tuberculosis, although 74% identical, have different residues in their active site clefts and allow the effects of amino acid substitutions to be assessed in understanding inhibitory potency. In addition, we have used the piperidinol 3-dimensional shape and electrostatic properties to identify two additional distinct chemical scaffolds as inhibitors of NAT. While one of the scaffolds has anti-tubercular activity, both inhibit NAT but through a non-covalent mechanism. Full article

An efficient synthesis of a highly potent and selective IP (PGI₂ receptor) agonist that is not structurally analogous to PGI₂ is described. This synthesis is accomplished through the following key steps: Nucleophilic ring-opening of 3-(4-chlorophenyl)-oxazolidin-2-one prepared by a one-pot procedure with 4-piperidinol and selective O-alkylation of 1-(2-(4-chlorophenylamino)ethyl)piperidin-4-ol. The obtained compound is a potent and selective IP agonist displaying a long duration of action. Full article

The efficient transformation of D-glucal to (2R)-hydroxymethyldihydro-pyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+)-desoxoprosophylline (1) and deoxymannojirimycin (3) or D-mannolactam (4), respectively. Full article

Bis (2,2,6,6-tetramethyl-4-piperidinyl) maleate is a key intermediate for the synthesis of new types of hindered amine light stabilizers (HALS), so new synthetic routes to this compound are desirable. Through an orthogonal design and follow-up single factor experiments optimal reaction conditions were determined for synthesizing bis (2,2,6,6-tetramethyl-4-piperidiny) maleate using dimethyl maleate, 2,2,6,6-tetramethyl-4-piperidinol and zeolite supported tetraisopropyl titanate as catalyst. Under the selected conditions, the reaction rate and the yield are high, the selectivity is good, the catalyst can be recycled, and there are fewer wastes. The product was characterized and quantitatively analyzed by elemental analysis, mass spectrometry, infrared spectroscopy, nuclear magnetic resonance spectroscopy and ion suppression chromatography. Full article