Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives

Abstract

Subtype-selective α-adrenoceptor (AR) antagonists display optimum therapeutic efficacies for the treatment of benign prostatic hyperplasia (BPH). In this study, we designed and synthesized novel carbazole-arylpiperazines derivatives (1 and 2) on the basis of the proposed pharmacophore model for α-AR antagonists. Structural properties were investigated using single-crystal X-ray diffraction analysis. Comparison of crystal structures with ligand-based pharmacophore models revealed that the two agents may possess antagonistic effects on α subtype. Tissue functional assay in vitro showed that compound 2 exerted strong antagonistic activity on α-AR (pA 7.13) with a poor selectivity for α and α subtypes. Compound 1 exhibited enhanced antagonistic effect on α subtype (pA 7.06) and excellent selectivity for α over α (α/α ratio=79.4). To illustrate the relationship between antagonistic activity and chemical structure, molecular docking studies were performed using the homology models of α receptors. Binding mechanism indicated that small hydrophobic substituents attached to the arylpiperazine moiety were essential for rational design of α-selective antagonists.

Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of Enterococcus faecalis

“…It has been reported that the introduction of a hydroxy group as hydrogen bond donor to carbazole derivatives could ameliorate physicochemical property and improve binding affinity with bioactive molecules, thus enhancing biological activities. 13 Alcohols from natural and artificial sources have long been employed as disinfectants with potent antimicrobial potentiality in daily life because of the ubiquity, convenience, and high efficiency. 14 Particularly, aminoalcohols have been announced to exert prominent antibacterial abilities.…”

“…However, the poor solubility of carbazole, which is probably resulted from the rigidly planar structure, has imposed serious restriction on its further application. It has been reported that the introduction of a hydroxy group as hydrogen bond donor to carbazole derivatives could ameliorate physicochemical property and improve binding affinity with bioactive molecules, thus enhancing biological activities …”

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

“…Molecular docking was performed on α 1D receptor constructed by homology model building using the AutoDock-vina program since the accurate 3D structures of α 1D -AR with high resolutions has not been obtained yet 12 . To achieve the reliable docking results, the lowest energy conformations of NAF enantiomers were extracted from their crystal structures and the α 1D -AR model was submitted to be energy optimization by using CHARMMing program.…”

“…The homology model of α 1D subtype was successfully produced by our previous work 12 , and then submitted to be energy optimization by using CHARMMing program. Structural evaluation and stereochemical analyses were performed using PROCHECK, PROVE, CRYST and Ramchandran plot 13 .…”

Synthesis, Antimicrobial Screening and In Silico Appraisal of Iminocarbazole Derivatives

“…The antibacterial activity observed for murrayanine, extracted from the stem bark of Murraya Koenigii (Rutaceae), unravels the new era for the development of carbazole‐based scaffolds for pharmaceutical applications . Carbazole motifs demonstrate versatile pharmacological activities, such as 5‐HT 7 R blocking activity (VII), antibacterial, anti‐oxidant, antidiabetic, antifungal, antihistaminic, neuroprotective, antitumor, antiviral, antitubercular, antipsychotic and anticonvulsant activities –. Glycozoline (I) like carbazole alkaloids were reported for their antibiotic activity .…”