CHARACTERIZATION OF NOVEL CARPROFEN DERIVATIVES AS INHIBITORS OF THE SEROTONIN 5-HT2C RECEPTORS AND CLK4-KD PROTEIN KINASE FOR THE DEVELOPMENT OF PHARMACOLOGICALLY ACTIVE COMPOUNDS DOI Open Access
Ana-Maria Udrea

FARMACIA, Journal Year: 2023, Volume and Issue: 71(6), P. 1232 - 1240

Published: Dec. 28, 2023

In search of novel compounds with multiple biological activities, nine carprofen derivatives (1a-i) have been investigated by molecular docking to explore their interactions target proteins involved in different diseases, from cancer inflammation associated pathologies (viral infections, pain, neurodegenerative conditions).The studies performed study the dual specificity for protein kinase CLK4 and serotonin 2C (5-HT2C) receptor.Our predictions indicate that highest predicted binding energy has observed case 1b derivative 5-HT2C receptor respectively 1h CLK4-KD.Therefore, these two show a promising potential development multi-pharmacologically active compounds. RezumatÎn vederea descoperirii de noi compuși cu activități biologice multiple, nouă derivați ai carprofenului au fost investigați prin andocare moleculară pentru explora interacțiunile lor proteinele țintă implicate în diferite boli, la patologii asociate inflamației (infecții virale, durere, afecțiuni neurodegenerative).Studiile efectuate studia specificitatea duală receptorul proteinkinazei și cel al serotoninei (5-HT2C).Predicțiile noastre indică faptul că cea mai mare energie legare prezisă observată cazul derivatului și, respectiv, CLK4-KD.Prin urmare, acești doi arată un potențial promițător dezvoltarea compușilor farmacologic multivalent.

Antibacterial Potential of Tetrahydrocarbazoles (THCZ): A Review DOI
Nitin Kumar, Shalini Sharma, Saurabh Agrawal

et al.

Current Bioactive Compounds, Journal Year: 2024, Volume and Issue: 20(10)

Published: Feb. 7, 2024

: Antibiotic resistance has become a major public threat across the globe associated with human health. Some bacterial and fungal infections produce resistance, such as methicillinresistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) multidrug-resistant (MDR) species Acinetobacter baumannii etc. Tetrahydrocarbazoles (THCz) are sub-class of indole alkaloids profoundly present in natural products biologically active compounds have displayed potential biological activities literature. THCz exhibit antibacterial through pathways like cell wall synthesis inhibition DNA gyrase enzyme sliding clamp inhibitors MreB inhibitors. These THCZ also showed significant vitro against bacterial-resistant species, MRSA, VRE MTDL (Multi Target Direct ligand) approach been significantly used for design THC motif-based agents. In this review article, we collected literature on agent from 2014 to date. The study core-based derivatives found excellent profiles revealed that they can play role drug discovery development new antibiotics various infectious diseases.

Language: Английский

Citations

1
Benzocarbazoledinones as SARS-CoV-2 Replication Inhibitors: Synthesis, Cell-Based Studies, Enzyme Inhibition, Molecular Modeling, and Pharmacokinetics Insights DOI Creative Commons
Luana G. de Souza, Eduarda Alves Penna, Alice dos Santos Rosa

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(11), P. 1768 - 1768

Published: Nov. 13, 2024

Endemic and pandemic viruses represent significant public health challenges, leading to substantial morbidity mortality over time. The COVID-19 has underscored the urgent need for development discovery of new, potent antiviral agents. In this study, we present synthesis anti-SARS-CoV-2 activity a series benzocarbazoledinones, assessed using cell-based screening assays. Our results indicate that four compounds (4a, 4b, 4d, 4i) exhibit EC50 values below 4 μM without cytotoxic effects in Calu-3 cells. Mechanistic investigations focused on inhibition SARS-CoV-2 main protease (Mpro) papain-like (PLpro) have used enzymatic Notably, 4a 4b showed Mpro with IC50 0.11 ± 0.05 0.37 µM, respectively. Furthermore, silico molecular docking, physicochemical, pharmacokinetic studies were conducted validate mechanism assess bioavailability. Compound was selected preliminary drug-likeness analysis vivo pharmacokinetics investigations, which yielded promising corroborated vitro findings, reinforcing its potential as an lead compound.

Language: Английский

Citations

1
Special Issue “Carbazole Derivatives: Latest Advances and Prospects” DOI Creative Commons
Anna Caruso

Applied Sciences, Journal Year: 2023, Volume and Issue: 13(7), P. 4263 - 4263

Published: March 28, 2023

The academic community has extensively explored, over the years, heterocyclic compounds of carbazolic motif [...]

Language: Английский

Citations

1
Diastereoselective construction of carbazole‐based spiropyrrolidines and spiropyrrolizidines via cycloaddition reaction DOI

Panneerselvi Varadharajan,

Shankar Karikalan,

Kumaresan Prabakaran

et al.

Journal of Heterocyclic Chemistry, Journal Year: 2023, Volume and Issue: 60(12), P. 2081 - 2091

Published: Oct. 11, 2023

Abstract A series of new spiro heterocyclic compounds having carbazole and pyrrolidine units were successfully synthesized through a one‐pot, three component, 1,3‐dipolar cycloaddition reaction in good yields with high diastereoselectivity. Simple reaction, easily accessible chemicals, yield diastereoselective formation monospiropyrrolidine monospiropyrrolizidine derivatives one step are some advantages this method. The structure the obtained products was characterized by using spectroscopic techniques.

Language: Английский

Citations

1
The Potential of Indole Alkaloids in Bone Health and Osteoporosis Management DOI Creative Commons
Anna Caruso,

Virginia Caira,

Hussein El‐Kashef

et al.

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(18), P. 8124 - 8124

Published: Sept. 10, 2024

Indole alkaloids, a class of plant-derived nitrogen-containing compounds, have emerged as promising candidates for osteoporosis treatment. Their favorable biocompatibility profile demonstrated efficacy in preclinical models, and low reported toxicity make them attractive alternatives to existing therapies. This review focuses on the therapeutic potential specific indole including vindoline, rutaecarpine, harmine, its derivatives, promoting bone health managing osteoporosis.

Language: Английский

Citations

0
CHARACTERIZATION OF NOVEL CARPROFEN DERIVATIVES AS INHIBITORS OF THE SEROTONIN 5-HT2C RECEPTORS AND CLK4-KD PROTEIN KINASE FOR THE DEVELOPMENT OF PHARMACOLOGICALLY ACTIVE COMPOUNDS DOI Open Access
Ana-Maria Udrea

FARMACIA, Journal Year: 2023, Volume and Issue: 71(6), P. 1232 - 1240

Published: Dec. 28, 2023

In search of novel compounds with multiple biological activities, nine carprofen derivatives (1a-i) have been investigated by molecular docking to explore their interactions target proteins involved in different diseases, from cancer inflammation associated pathologies (viral infections, pain, neurodegenerative conditions).The studies performed study the dual specificity for protein kinase CLK4 and serotonin 2C (5-HT2C) receptor.Our predictions indicate that highest predicted binding energy has observed case 1b derivative 5-HT2C receptor respectively 1h CLK4-KD.Therefore, these two show a promising potential development multi-pharmacologically active compounds. RezumatÎn vederea descoperirii de noi compuși cu activități biologice multiple, nouă derivați ai carprofenului au fost investigați prin andocare moleculară pentru explora interacțiunile lor proteinele țintă implicate în diferite boli, la patologii asociate inflamației (infecții virale, durere, afecțiuni neurodegenerative).Studiile efectuate studia specificitatea duală receptorul proteinkinazei și cel al serotoninei (5-HT2C).Predicțiile noastre indică faptul că cea mai mare energie legare prezisă observată cazul derivatului și, respectiv, CLK4-KD.Prin urmare, acești doi arată un potențial promițător dezvoltarea compușilor farmacologic multivalent.

Citations

0