Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two π-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue.
In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a–d and 5g, possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi.
Twelve novel quinazolinone–pyrimidine hybrids were synthesized, of which some of them showed dual functions as DPP-4 inhibitors and anti-cancer agents.
Fifteen derivatives of spirooxindole-4H-pyran (A 1 -A 15 ) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A 3 and A 12 were the most active compounds and indicated signi cant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no signi cant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding a nities as γ-aminobutyric acid-A (GABA-A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.
Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral ((1) H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole.
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