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the current investigation, 109 known ERα inhibitors have been developed in the current research; pharmacophore modeling, Molecular docking, MM‐GBSA, and MD study have been performed to investigate the binding affinity of 9‐anilinoacridines with heterocyclic substitutes as selective ERα inhibitors for breast carcinoma. Pharmacophore model have been developed by Schrodinger suite 2019–2 phasemodule. To predict binding free energy of the ligands in complex with PDB and post docked energy minimization was performed by Prime, MM‐GB/SA module. The Induced fit docking studies were performed on the ligand modulated dynamic behaviour of the protein molecular dynamics study. A statistical substantial 3D ‐ QSAR design was created using the pharmacophore hypothesis. 109 known ERα inhibitors have been developed with pIC50 values between 4.0 and 6.0 and were used in ligand‐based pharmacophore modelling and 3D‐QSAR analysis. R2 (0.8294), Q2 (0.7~0.8), and F value (83.5) were used to statistically validate the developed five‐point hypothesis DHRRR1 employing a minimum square of four. Molecular dynamics simulations were run to comprehend the conformational changes and ligand stability at the protein active pocket. The predicted 3D‐QSAR model significantly correlated with experimentally reported in‐vitro antitumor activity. These in‐silico discoveries will help in the future search for potent ERα inhibitors with desirable pharmacophoric properties. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is one of the prevalent neurodegenerative disorders; it is generally characterized by sudden abruption of blood flow due to thromboembolism and vascular abnormalities, eventually impairing the supply of oxygen and nutrients to the brain for its metabolic needs. Oxygen-glucose deprived conditions provoke the release of excessive glutamate, which causes excitotoxicity. Summary: Recent studies suggest that circulatory angiotensin-II (Ang-II) has an imperative role in initiating detrimental events through binding central angiotensin 1 (AT1) receptors. Insufficient energy metabolites and essential ions often lead to oxidative stress during ischemic reperfusion, which leads to the release of proinflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cytokines like interleukin-18 (IL-18) and interleukin- 1beta (IL-1β). The transmembrane glutamate transporters, excitatory amino acid transporter-2 (EAAT-2), which express in astroglial cells, have a crucial role in the clearance of glutamate from its releasing site and convert glutamate into glutamine in normal circumstances of brain physiology. Key Message: During cerebral ischemia, an impairment or dysfunction of EAAT-2 attributes the risk of delayed neuronal cell death. Earlier studies evidencing that angiotensin receptor blockers (ARB) attenuate neuroinflammation by inhibiting the Ang-II/AT1 receptor-mediated inflammatory pathway and that ceftriaxone ameliorates the excitotoxicity-induced neuronal deterioration by enhancing the transcription and expression of EAAT-2 via the nuclear transcriptional factor kappa-B (NF-kB) signaling pathway. The present review will briefly discuss the mechanisms involved in Ang-II/AT1-mediated neuroinflammation, ceftriaxone-induced EAAT-2 expression, and the repurposing hypothesis of the novel combination of ARBs and ceftriaxone for the treatment of cerebral ischemia. [ABSTRACT FROM AUTHOR]

Since depression is a common mental illness affecting an estimated 5% of people worldwide, investigators are encouraged to develop effective antidepressants. According to the monoamine-deficiency hypothesis, the underlying pathophysiology of depression is a deficiency of some neurotransmitters (serotonin, norepinephrine, or dopamine) in the central nervous system. The neurotransmitter serotonin has drawn the most attention concerning depression. As per research, 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) elevates inter-synaptic serotonin levels when administered as a single inhalation of vapor from dried toad secretion and leads to higher life satisfaction, convergent thinking, higher ratings of mindfulness, lower ratings of depression, and anxiety. Furthermore, although 5-MeO-DMT lowers stress biomarkers such as cortisol, it is a psychedelic with hallucinogenic effects. In the present study, analogues of 5-MeO-DMT are designed with the hope that they might have better therapeutic activity and lower psychedelic side effects. The current study aimed to look at 5-MeO-DMT analogues as possible antidepressants. We used 70,000 5-MeO-DMT analogues that were sketched using Marvin to conduct a High Throughput Virtual Screening method in hopes of finding potential 5-MeO-DMT analogues against the 5-Hydroxytryptamine 1A receptor (5-HT1AR; 7E2Y.pdb) as an agonist. The prediction of the analogue-protein interaction and the evaluation of the binding affinity is accomplished by employing molecular docking. The Glide XP docking data indicated that a total of 21 compounds had Glide gscores ranging from - 11.41 to -6.53 kcal/mol. When compared to the standard 5-MeO-DMT with the binding affinity of -7.75 kcal/mol, 14 compounds showed better binding affinity. Furthermore, Molecular Mechanics -Generalised Born and Surface Area solvation (MM-GBSA) indicated a binding free energy range of -63.55 to -35.37 kcal/mol, and 18 compounds showed better binding free energy than standard 5-MeO-DMT (-41.42 kcal/mol). Through ligand binding interactions with Asp116, Phe361, Phe362, Ser190, Ser199, Val117, Trp358, Ala365, Pro369, Ile189, Tyr195, Ala203, Ile167, Tyr390, Cys120, Trp358, Val364, Ala365, and Leu368, these complexes were stabilized, according to the molecular dynamic simulation of 20453/7E2Y in 100ns. [ABSTRACT FROM AUTHOR]

Introduction: Isoflavones are plant derived chemical substances and are called as phytoestrogens. These are present in different parts of the plants belongs to legumes family and chemical structures are resembled with endogenously available female reproductive hormone estradiol. Isoflavones exerts their biological actions by activates estrogen receptors as estradiol. Methods: The in-silico docking studies were performed for isoflavone compounds as ERa (Estrogen Receptor Alpha) (PDB ID-2IOG) activators targeting cardiovascular diseases using Schrodinger suite 2019-2, Maestro 9.6 version. Docking against ERa was performed using glide module, in silico ADMET screening by qikprop module and free binding energy by prime MMGBSA module. Results: The binding affinity of the compounds towards ERa was selected by glide score and interaction patterns. Many compounds showed strong hydrophobic interactions and hydrogen bonding interactions to activate ERa as standard substance estradiol. The compounds sissotrin, artocarpin, warangalone, puerarin, alpinum and luteone have good binding affinity with glide scores -11.91, -11.68, -11.55, -11.43, -11.26 and -11.10 respectively when compared with standard compound i.e estradiol glide score was -9.85. The ADMET properties are with in recommended values. MMGBSA binding results of the most potent activators are favourable. Conclusion: The compounds sissotrin, artocarpin, warangalone, puerarin, alpinum and luteone with good glide scores may produce significant cardioprotective activity like estradiol and further in in vitro and in vivo investigations. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the leading diseases in men all over the world caused due to over-expression of prostate-specific membrane antigen (PSMA). Currently, the detection and targeting of PCa is one of the major challenges in the prostate gland. Therefore, Bruton tyrosine kinase inhibitor molecules like ibrutinib (Ibr) loaded with nanomaterials like multiwalled carbon nanotubes (MWCNTs), which has good physico-chemical properties may be the best regimen to treat PCa. In this strategy, the chemically modified MWCNTs have excellent 'Biosensing' properties makes it easy for detecting PCa without fluorescent agent and thus targets particular site of PCa. In the present study, Ibr/MWCNTs conjugated with T30 oligonucleotide may selectively target and inhibit PSMA thereby reduce the over-expression in PCa. Hence, the proposed formulation design can extensively reduce the dosage regimen without any toxic effect. Additionally, the present hypothesis also revealed the binding mode of Ibr in the catalytic pocket of PSMA by in silico method. Therefore, we presume that if this hypothesis proves correct, it becomes an additional novel tool and one of the conceivable therapeutic options in treating PCa. [ABSTRACT FROM AUTHOR]

Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae) is the most important plant in the herbal remedies. The present study focus on the isolation, in-silico and in-vitro studies of the two alkaloids C1 (5-(4-[(methylcarbamoyl) amino]-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl methyl carbamate is novel alkaloid and C2 13-Docosenamide is a known alkaloid. The chemical structures of compounds have been elucidated based on comprehensive techniques like GCMS, IR and NMR. In order to know the molecular mechanisms for the two compounds, in silico molecular docking study has been performed. Both compounds have shown perfect binding affinity to the enzymes TNF α, IL-4, IL-13 and 5 LOX Enzyme. The compounds also exhibited comparable G-scores and Glide energy values in comparison with the standard dexamethasone. In addition both the compounds have been tested for in vitro antioxidant assay by using ABTS and DPPH method and the results were compared with standard ascorbic acid. [ABSTRACT FROM AUTHOR]

Monosodium glutamate (MSG) is one of famous flavoring agents and mainly used in many commercially packed food, restaurant and domestic cooking. Continuous eating of MSG is always associated with general weakness, neuronal damage, depression, stress, learning troubles in healthy human beings. Recent studies reported injurious effects of neurotoxicity produced by excess MSG was countered by medicines from herbal origin. The main aim of this work was to probe the neuroprotective activity of the ethanolic extract of Tribulus terrestris leaves against the MSG induced nervous degeneration in albino rats. The rats were given with EETT at drug dose of 100, 200 and 400 mg/kg and memantine at 20 mg/kg every day for about 7 d. On all the days, the MSG was given an h before the drugs treatment. The rats were noticed for changes in the neurological behaviour on all 7 d. EETT and MMT administration dominantly enhanced the general overall behavior, locomotor activity & lowering in the stagnant time when compared with group treated with MSG. In addition to this, EETT were found to normalize the glutathione content (GSH), catalase content (CAT), superoxide dismutase content (SOD), monoamines neurotransmitter such as norepinephrines (NE) and 5-hydroxytryptamine (5-HT), reduction in the elevated level of lipid peroxidation (LPO) and acetylcholinesterases (AChE). This research outcome suggests that EETT contains phytoconstituents like flavonoids and phenolic compounds that may have efficacy in the averting the neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Breast cancer, a most common cancer in the women worldwide representing about quarter (25%) of all cancers. The predictions of cancer prevalence show an imperative need for strengthening the present diagnostic/treatment facilities. One such strategy to overcome the treatment burden for the breast cancer is drug repurposing/repositioning. This concept has been growing its importance, the very reason behind this is it decreases significantly the funds needed for the development of therapy for a disease and it increases the chances of the new indications from Phase I to entry in the market. The objective of the study was to evaluated the morphological characteristic, migration features of the cells and cell cycle arrest of the anti-HSV drug Acyclovir against breast cancer cell lines MCF-7 and MDA-MB231. The in vitro cytotoxicity studies, fragmentation assay, long term clonogenic assay and cell cycle analysis were carried out in the study. In MTT assay acyclovir showed IC50 of 3.16 ± 1.10 µg/ml and 3.85 ± 1.54µg/ml respectively with SI of 33.46 tested against MCF-7 and MDAMB-231 cell lines. The platting efficiency was found to be 52.30 % by clonogenic assay. One of the indications of cell death by apoptosis is accumulation of cells in G2/M phase which was observed with Acyclovir in cell cycle analysis. The study showed that Acyclovir inhibited cancer cells propagation, colony formation ability and cell cycle arrest at G2/M phase, while having no effect on the normal cells. These results indicated new insights on the effect of anti-HSV agents on the tumorigenesis and metastasis. [ABSTRACT FROM AUTHOR]