Synthesis, human carbonic anhydrase I and II inhibition, and in silico studies of 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate derived thiosemicarbazones.

This study describes the synthesis and biological evaluation of 2-ethoxy-6-formylphenyl [1,1'-biphenyl]-4-sulfonate-based thiosemicarbazones 5(a-s) as potential inhibitors of human carbonic anhydrase isoforms hCA I and hCA II. Among the synthesized compounds, 5 k exhibited potent inhibition, with IC values of 89.25 nM and 54.

Design, Synthesis, In Vitro, and In Silico Studies of 5-(Diethylamino)-2-Formylphenyl Naphthalene-2-Sulfonate Based Thiosemicarbazones as Potent Anti-Alzheimer Agents.

Alzheimer's disease (AD) is known as one of the more devastating neurodegenerative diseases diagnosed in older people. Cholinesterase inhibitors (ChEI) can be used as an effective palliative treatment for AD. An extensive range of new biologically active 4-(diethylamino) salicylaldehyde-based thiosemicarbazone derivatives 5(a-u) was synthesized and evaluated as inhibitors of cholinesterase (ChE) and monoamine oxidase (MAO) enzymes.

Synthesis, Anti-Alzheimer Evaluation and In Silico Study of 4-Methoxyphenyl)Sulfonyl Indole Hybrid Thiosemicarbazones.

Alzheimer's disease (AD) is a multifaceted neurological disorder linked to behavioral, psychological, and language abnormalities as well as memory loss. A series of 1-[(4-methoxyphenyl)sulfonyl]-1H-indole-3-carbaldehyde-based thiosemicarbazones 5(a-v) had been synthesized and screened for their potential against AD. The compounds were tested for their inhibitory effects against cholinesterases (AChE and BChE) and monoamine oxidase A (MAO-A).

and analysis of synthesized -benzyl indole-derived hydrazones as potential anti-triple negative breast cancer agents.

Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and it is characterized by a high recurrence rate and the rapid development of drug resistance across various subtypes. Currently, there is no targeted therapy, which is specifically approved for the treatment of TNBC. In this study, we synthesized a series of -benzyl indole-3-carboxaldehyde-based hydrazones and subjected them to anticancer studies on MCF-10A and MDA-MB-231 breast cancer (BC) cell lines.

Synthesis, in vitro, and in silico studies of 7-fluorochromone based thiosemicarbazones as α-glucosidase inhibitors.

Increased blood sugar is a typical manifestation of Type-2 Diabetes Mellitus (T2DM), a metabolic disorder that can be effectively managed with the help of α-glucosidase inhibitors. A range of new chromone based thiosemicarbazone derivatives (3a-t) was synthesized and assessed due to their ability to suppress α-glucosidase in this research. Having IC values spanning from 6.

Analyzing Oxygen Atom Distribution in FDA-Approved Drugs to Enhance Drug Discovery Strategies.

Despite advancements in molecular design rules and understanding biochemical processes, the field of drug design and discovery seeks to minimize the number and duration of synthesis-testing cycles to convert lead compounds into drug candidates. A promising strategy involves gaining insightful understanding of key heteroatoms such as oxygen and nitrogen. This work presents a comprehensive analysis of oxygen atoms in approved drugs, aiming to streamline drug design and discovery efforts.

Synergizing GA-XGBoost and QSAR modeling: Breaking down activity aliffs in HDAC1 inhibitors.

The work being presented now combines severe gradient boosting with Shapley values, a thriving merger within the field of explainable artificial intelligence. We also use a genetic algorithm to analyse the HDAC1 inhibitory activity of a broad pool of 1274 molecules experimentally reported for HDAC1 inhibition. We conduct this analysis to ascertain the HDAC1 inhibitory activity of these molecules.

Design, synthesis, QSAR modelling and molecular dynamic simulations of N-tosyl-indole hybrid thiosemicarbazones as competitive tyrosinase inhibitors.

Tyrosinase is an enzyme crucial for the progression of melanogenesis. Immoderate production of melanin may be the cause of hyperpigmentation and darkening leading to skin diseases. Tyrosinase is the most researched target for suppressing melanogenesis since it catalyzes the rate-limiting stage of melanin production.

Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors.

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors.

Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a approach.

Background: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline.

Synthesis and antiproliferative evaluation of novel 3,5,8-trisubstituted coumarins against breast cancer.

This study focused on designing and synthesizing novel derivatives of 3,5,8-trisubstituted coumarin. The synthesized compounds, particularly compound , exhibited significant cytotoxic effects on MCF-7 cells, surpassing staurosporine, and reduced toxicity toward MCF-10A cells, highlighting potential pharmacological advantages. Further, compound altered the cell cycle and significantly increased apoptosis in MCF-7 cells, involving both early (41.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC value of 0.

Computational Exploration of Naturally Occurring Flavonoids as TGF-β Inhibitors in Breast Cancer: Insights from Docking and Molecular Dynamics Simulations and In-vitro Cytotoxicity Study.

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-β) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-β inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation.

Chemical Composition of L. Cultivar Guajarina Essential Oils and Their Biological Activity.

The essential oils and aroma derived from the leaves (L), stems (St), and spikes (s) of L. cv. Guajarina were extracted; the essential oils were extracted using hydrodistillation (HD), and steam distillation (SD), and the aroma was obtained by simultaneous distillation and extraction (SDE).

Natural compounds for oxidative stress and neuroprotection in schizophrenia: composition, mechanisms, and therapeutic potential.

Objective: An imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms is believed to be a critical factor in the development of schizophrenia (SCZ) like neurological illnesses. Understanding the roles of ROS in the development of SCZ and the potential activity of natural antioxidants against SCZ could lead to more effective therapeutic options for the prevention and treatment of the illness.

Methods: SCZ is a mental disorder characterised by progressive impairments in working memory, attention, and executive functioning.

Mechanistic QSAR modeling derived virtual screening, drug repurposing, ADMET and - evaluation to identify anticancer lead as lysine-specific demethylase 5a inhibitor.

A lysine-specific demethylase is an enzyme that selectively eliminates methyl groups from lysine residues. KDM5A, also known as JARID1A or RBP2, belongs to the KDM5 Jumonji histone demethylase subfamily. To identify novel molecules that interact with the LSD5A receptor, we created a quantitative structure-activity relationship (QSAR) model.

Application of in-silico drug discovery techniques to discover a novel hit for target-specific inhibition of SARS-CoV-2 Mpro's revealed allosteric binding with MAO-B receptor: A theoretical study to find a cure for post-covid neurological disorder.

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection.

Carbonylbis(hydrazine-1-carbothioamide) derivatives as a new class of α-glucosidase inhibitors and their mechanistic insights via molecular docking and dynamic simulations.

In the past, efforts have been made to find a cure for diabetes, mainly evaluating new classes of compounds to explore their potency. In this study, we present the synthesis and evaluation of carbonylbis(hydrazine-1-carbothioamide) derivatives as potential α-glucosidase inhibitors, employing both in vivo and in silico investigations. The in vitro experiments revealed that all tested compounds were significantly potent for α-glucosidase inhibition, with the lead compound 3a displaying approximately 80 times higher activity than acarbose.

QSAR modeling approaches to identify a novel ACE2 inhibitor that selectively bind with the C and N terminals of the ectodomain.

Due to the high rates of drug development failure and the massive expenses associated with drug discovery, repurposing existing drugs has become more popular. As a result, we have used QSAR modelling on a large and varied dataset of 657 compounds in an effort to discover both explicit and subtle structural features requisite for ACE2 inhibitory activity, with the goal of identifying novel hit molecules. The QSAR modelling yielded a statistically robust QSAR model with high predictivity (R=0.

In-silico studies to recognize repurposing therapeutics toward arginase-I inhibitors as a potential onco-immunomodulators.

Rudolf Virchow was the first person to point out the important link between immune function and cancer. He did this by noticing that leukocytes were often found in tumors. Overexpression of arginase 1 (ARG1) and inducible nitric oxide synthase (iNOS) in myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs) depletes both intracellular and extracellular arginine.

Theoretical and Anti- Evaluations of Substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide and Imidazopyridine Hydrazide Derivatives.

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as H-NMR, C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against and suggested that all compounds essentially exhibited activity against selected strains of bacteria.

Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of β-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave β-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of β-amyloid-containing neurotic plaques, the characteristics of AD.