Design, synthesis and evaluation of 1-(1,5-bis(4-substituted phenyl)-2-methyl-1H-pyrrol-3-yl)-N-methylmethanamines as SERT inhibitors with potential antidepressant action.

BM212 is a potent anti-TB agent with pharmacophoric features similar to the antidepressant drug sertraline. The shape-based virtual screening of the DrugBank database on BM212 resulted in the identification of several CNS drugs with appreciable Tanimoto scores. The docking simulations also ascertained the selectivity of BM212 towards the serotonin reuptake transporter protein (SERT) with a docking score of -6.51 kcal mol-1. Based on the SAR data available for sertraline and other antidepressant drugs, we designed, synthesized and screened twelve 1-(1,5-bis(4-substituted phenyl)-2-methyl-1H-pyrrol-3-yl)-N-methylmethanamines (SA-1 to SA-12) for in vitro SERT inhibition and in vivo antidepressant activity. The compounds were screened for in vitro 5HT reuptake inhibition using the platelet model. Among the screened compounds, (1-(1,5-bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)-N-methylmethanamine) showed the same serotonin uptake inhibition (absorbance 0.22) as that of the standard drug sertraline (absorbance 0.22). BM212 had an effect on 5-HT uptake, albeit a weaker one compared to the standard (absorbance 0.671). Further, SA-5 was screened for in vivo antidepressant activity using the unpredictable chronic mild stress (UCMS) protocol to induce depression in mice. The effect of BM212 and SA-5 on the behaviour of the animals was assessed and compared against the standard drug sertraline. SA-5 at 20 mg per kg body weight was found to have a statistically significant impact on the behaviour of depressed animals.

Nannochloropsis Extract-Mediated Synthesis of Biogenic Silver Nanoparticles, Characterization and In Vitro Assessment of Antimicrobial, Antioxidant and Cytotoxic Activities.

Objective: To investigate the biogenic synthesis of silver nanoparticles (AgNPs) using partially purified ethyl acetate extract of Nannochloropsis sp. hexane (EAENH) fraction of microalga. Methods: The green synthesis of AgNPs was confirmed with UV-Vis spectrum which shows the surface plasmon resonance (SPR) at 421 nm. Fourier Transform Infrared Spectra (FTIR) presented the involvement of functional groups like carboxyl groups of fatty acids, tetraterpenoids of xanthophylls, hydroxyl groups of polyphenols, carbonyl and amide linkage of proteins in the AgNP synthesis. Gas Chromatography-Mass Spectrometry analysis (GCMS) revealed that phytochemicals like octadecanoic acid and hexadecanoic acid imply in capping, bioreduction, and stabilization of AgNps. Result: High-resolution Transmission electron microscope (HRTEM), Dynamic light scattering (DLS), X-ray diffraction (XRD) and EDX analysis showed the crystalline form of the AgNPs with Z-average size 57.25 nm. The zeta potential value of -25.7 mV demonstrated the negative surface charge and colloidal stability of AgNPs. The antimicrobial activity of AgNPs displayed effective inhibition zone against selected bacterial and fungal pathogens. In vitro, antioxidant effects were assessed by 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydrogen peroxide and reducing power assays which revealed excellent scavenging potential for AgNPs than the extracts. The anti-proliferative potential of biofabricated AgNPs and extracts on Human Non-small lung cancer cell line (A549) was assessed using 3­(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay with IC50 values of 15 µgmL-1 and 175 µgmL-1 respectively. Conclusion: The study reveals that the microalgae-mediated AgNPs possesses potent antimicrobial and antioxidant activity along with the ability to stimulate apoptosis in A-549 cell line.

Vitis vinifera (Muscat Variety) Seed Ethanolic Extract Preserves Activity Levels of Enzymes and Histology of the Liver in Adult Male Rats with Diabetes.

The effect of V. vinifera seeds on carbohydrate metabolizing enzymes and other enzymes of the liver in diabetes is currently unknown. We therefore investigated changes in the activity levels of these enzymes following V. vinifera seed extract administration to diabetic rats. Methods. V. vinifera seed ethanolic extract (250 and 500 mg/kg/day) or glibenclamide (600 µg/kg/day) was administered to streptozotocin-induced male diabetic rats for 28 consecutive days. At the end of treatment, liver was harvested and activity levels of various liver enzymes were determined. Levels of thiobarbituric acid reactive substances (TBARS) were measured in liver homogenates and liver histopathological changes were observed. Results. V. vinifera seed ethanolic extract was able to prevent the decrease in ICDH, SDH, MDH, and G-6-PDH and the increase in LDH activity levels in liver homogenates. The seed extract also caused serum levels of ALT, AST, ALP, ACP, GGT, and total bilirubin to decrease while causing total proteins to increase. Additionally, the levels of ALT, AST, and TBARS in liver homogenates were decreased. Histopathological changes in the liver were reduced. Conclusion. Near normal activity levels of various enzymes and histology of the liver following V. vinifera seed ethanolic extract administration may be due to decrease in liver oxidative stress in diabetes.