A5089166509- Drug Transport and Resistance Mechanisms
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Pharmacological Effects and Toxicity Studies
- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Computational Drug Discovery Methods
- Neurotransmitter Receptor Influence on Behavior
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Metal complexes synthesis and properties
- Trace Elements in Health
- RNA Interference and Gene Delivery
- Synthesis and Biological Evaluation
- Cholinesterase and Neurodegenerative Diseases
- DNA and Nucleic Acid Chemistry
- Adenosine and Purinergic Signaling
- Inflammatory mediators and NSAID effects
- Tryptophan and brain disorders
- Radiopharmaceutical Chemistry and Applications
- Chemical Reaction Mechanisms
University of Bari Aldo Moro
2016-2025
Wadsworth Center
2023
New York State Department of Health
2023
Mario Negri Institute for Pharmacological Research
2008
In this paper, we present a deep learning algorithm for automated design of druglike analogues (DeLA-Drug), recurrent neural network (RNN) model composed two long short-term memory (LSTM) layers and conceived data-driven generation similar-to-bioactive compounds. DeLA-Drug captures the syntax SMILES strings more than 1 million compounds belonging to ChEMBL28 database and, by employing new strategy called sampling with substitutions (SWS), generates molecules starting from single user-defined...
Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG leading cause of death for pediatric brain tumors due its infiltrative nature inoperability. Radiotherapy has only palliative effect on stabilizing symptoms.
In this paper, we introduce DeLA-DrugSelf, an upgraded version of DeLA-Drug [J. Chem. Inf. Model. 62 (2022) 1411-1424], which incorporates essential advancements for automated multi-objective de novo design. Unlike its predecessor, relies on SMILES notation molecular representation, DeLA-DrugSelf employs a novel and robust representation string named SELFIES (SELF-referencing embedded string). The generation process in not only involves substitutions to the initial representing starting...
Emerging evidence has demonstrated that cannabinoid receptor 2 (CB2) is involved in a number of diseases, such as neurodegenerative disorders and various types cancer, making it an attractive pharmacological target. Classically, protein active site or orthosteric binding site, where the endogenous ligand binds to, used target for design most small-molecule drugs. This can present challenges when comes to phylogenetically related proteins have similar sites, receptors. An alternative approach...
Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis cereus as potent selective bactericides. Biological studies the synthesized...
Abstract With the aim of contributing to development novel antitumor agents, high‐affinity σ 2 receptor agonists were developed, with 6,7‐dimethoxy‐2‐[4‐[1‐(4‐fluorophenyl)‐1 H ‐indol‐3‐yl]butyl]‐1,2,3,4‐tetrahydroisoquinoline ( 15 ) and 9‐[4‐(6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinolin‐2‐yl)butyl]‐9 ‐carbazole 25 showing exceptional selectivity for subtype. Most compounds displayed notable antiproliferative activity in human MCF7 breast adenocarcinoma cells, similar corresponding...
Starting from the previously reported 5-HT 7 receptor agents 4-7 with N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinehexanamide structure, 1-(2-methylthiophenyl)-, 1-(2-diphenyl)-, 1-(2-isopropylphenyl)-, and 1-(2-methoxyphenyl)piperazine derivatives 8-31 were designed primary aim to obtain new compounds endowed suitable physicochemical properties for rapid extensive penetration into brain. The affinities 7, 1A, D 2 receptors of assessed, several displayed in nanomolar range. Among...
Several 1-cyclohexylpiperazine derivatives related to σ2 receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (33, Ki = 0.34 nM) were synthesized and tested in radioligand binding assays, attempt a structure−affinity relationship study. Intermediate alkyl chain length methoxyl group position on the tetralin nucleus varied. A few naphthalene analogues also prepared. High affinities found for almost all compounds, some of which displayed values...
A series of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides was prepared and their affinity for serotonin (5-hydroxytryptamine, 5-HT) 5-HT7, 5-HT(1A), 5-HT(2A) receptors measured by in vitro binding assays. In relation to 5-HT7 receptor affinity, studies indicated that (i) the optimal alkyl chain length five methylenes, (ii) an unsubstituted 1,2,3,4-tetrahydronaphthalenyl nucleus preferred, (iii) substitution pattern aryl ring linked piperazine played a crucial role....
Here we report the synthesis of N-(1,2,3,4-tetrahydronaphthalen-1-yl)-4-aryl-1-piperazinealkylamides 16−29 that were designed to elucidate both structure−affinity and −activity relationships for 5-HT7 receptor, by targeting substituent in 2-position aryl linked piperazine ring. The affinities 5-HT7, 5-HT1A, 5-HT2A, D2 receptors assessed radioligand binding assays. intrinsic activities at receptor most potent compounds determined. A series substituents covering a wide range electronic,...
Abstract The 2‐aryloxazole and 2‐arylthiazole scaffolds were used for generating compounds that we characterized their inhibitory activity toward ATP binding cassette transporters involved in multi‐drug resistance, such as BCRP MRP1, by using tumor cell lines overexpressing each transporter. These SAR studies are a significant step improving the potency against P‐glycoprotein, BCRP, MRP1. magnified image 2‐Aryloxazole derivatives evaluated P‐glycoprotein (P‐gp) well selectivity other ABC...