Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking,Lipid-Mediated Molecular Dynamics,and In Vivo Analysis

Background: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. Methods: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. Results: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. Conclusions: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.     

Design,Sustainable Synthesis and Biological Evaluation of a Novel Dual α2A/5-HT7 Receptor Antagonist with Antidepressant-Like Properties

The complex pathophysiology of depression, together with the limits of currently available antidepressants, has resulted in the continuous quest for alternative therapeutic strategies. Numerous findings suggest that pharmacological blockade of α₂-adrenoceptor might be beneficial for the treatment of depressive symptoms by increasing both norepinephrine and serotonin levels in certain brain areas. Moreover, the antidepressant properties of 5-HT₇ receptor antagonists have been widely demonstrated in a large set of animal models. Considering the potential therapeutic advantages in targeting both α₂-adrenoceptors and 5-HT₇ receptors, we designed a small series of arylsulfonamide derivatives of (dihydrobenzofuranoxy)ethyl piperidines as dually active ligands. Following green chemistry principles, the designed compounds were synthesized entirely using a sustainable mechanochemical approach. The identified compound 8 behaved as a potent α_2A/5-HT₇ receptor antagonist and displayed moderate-to-high selectivity over α₁-adrenoceptor subtypes and selected serotonin and dopaminergic receptors. Finally, compound 8 improved performance of mice in the forced swim test, displaying similar potency to the reference drug mirtazapine.     

A Study on Deletion in Polymer Region of Amelogenin (Amel Y) Gene: Significant Importance in Sex Determination and Identification of Sexual Assault Perpetrator

Accurate gender determination is crucial in many scientific disciplines, especially in prenatal diagnosis of X-linked diseases and forensic investigations. Today, molecular techniques, especially typing for a length variation in the X–Y homologous amelogenin gene (AMEL X and AMEL Y), are used for gender assignation. This amelogenin is an integral part of most PCR multiplex kits for gender determination marker, but in 1998 there was a report of two normal males being typed as female with this marker. Subsequently, a small number of males with amelogenin deleted genes have been reported in various populations but little data are available characterizing these deletions. This review aims to explore possible relationships among the AMEL Y deleted samples and Y-chromosome microsatellite haplotypes. Also, attempts are made to determine the frequency of males with AMEL Y deleted gene in various countries across the globe. Although some studies have shown that males with AMEL Y deleted gene are extremely rare in most populations, typing an additional gender-determining locus should be considered in forensic investigations where the reference sample is of unknown gender.