Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells DOI Open Access
Atikul Islam,

Xiao Chi Chen,

Chia-Wei Weng

et al.

Published: Aug. 25, 2023

The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus , has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, drug targets remained unknown. In this study, we conducted cellular thermal shift assays and molecular docking simulations identify validate intracellular water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH), p53-functional SAS p53-mutated HSC-3 oral cancer cells. Consistent with our silico studies, (CETSA) revealed that, addition SIRT1, 4-dmH preferentially targeted a tumor-associated NADH oxidase called tNOX or ENOX2. direct binding inhibited activity enhanced ubiquitin-proteasomal protein degradation both Moreover, inhibition decreased oxidation NAD + diminished -dependent SIRT1 deacetylase activity, ultimately inducing apoptosis significant cytotoxicity cell types. We also observed upregulated tumor tissues patients compared adjacent normal tissues, suggesting their relevance. Finally, better therapeutic efficacy confirmed tumor-bearing mice, greater downregulation volume reduction when treated heliomycin. Taken together, vitro vivo findings suggest multifaceted properties enable it offer superior antitumor value parental heliomycin, indicated functions through targeting tNOX-NAD -SIRT1 axis induce

Language: Английский

Exploration of Indolo[3,2c]isoquinoline derived triazoles as potential antimicrobial and DNA cleavage agents: Synthesis, DFT calculations, and molecular modeling studies DOI

Suliphuldevarada Mathada Basavarajaiah,

Jaishree Badiger,

Nagesh Gunavanthrao Yernale

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 137, P. 106598 - 106598

Published: May 9, 2023

Language: Английский

Citations

25
Exploration of novel isoniazid embedded 1,3,4-oxadiazole hybrids as anti-TB, antioxidant, and COX inhibitors: synthesis, spectral analysis, and molecular modeling studies DOI

S. Jisha,

Nagesh Gunavanthrao Yernale,

Prashantha Karunakar

et al.

Journal of the Iranian Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

Citations

1
Naphtho[2,1-b]furan derived triazole-pyrimidines as highly potential InhA and Cytochrome c peroxidase inhibitors: Synthesis, DFT calculations, drug-likeness profile, molecular docking and dynamic studies DOI

D.L. Roopa,

K. Shyamsunder,

Prashantha Karunakar

et al.

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1287, P. 135685 - 135685

Published: April 29, 2023

Language: Английский

Citations

22
Novel pyrimidines as COX-2 selective inhibitors: synthesis, DFT analysis, molecular docking and dynamic simulation studies DOI

Basavarajaiah Suliphuldevara Mathada,

N. Jeelan Basha,

Mohammad Javeed

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(4), P. 1751 - 1764

Published: April 27, 2023

Pyrimidine and its derivatives are associated with varieties of biological properties. Therefore, we herein reported the synthesis four novel pyrimidines (2, 3, 4a, b) derivatives. The structure these molecules is confirmed by spectroscopic methods such as IR, NMR, Mass analysis. electronic behavior synthesized compounds b in silico drug design 4 c, d was explained Density Functional Theory estimations at DFT/B3LYP level via 6-31 G++ (d, p) replicates geometry. All were screened for their vitro COX-1 COX-2 inhibitory activity compared to standards Celecoxib Ibuprofen. Compounds 3 4a afforded excellent activities IC50 = 5.50 5.05 μM against COX-1, 0.85 0.65 COX-2, respectively. standard drugs Ibuprofen showed 6.34 3.1 0.56 1.2 Further, high potential docking SARS-CoV-2 Omicron protease & predicted drug-likeness pyrimidine analogs using Molinspiration. protein stability, fluctuations APO–protein, protein–ligand complexes investigated through Molecular Dynamics simulations studies Desmond Maestro 11.3 lead identified.Communicated Ramaswamy H. Sarma

Language: Английский

Citations

21
Synthesis, Structural Investigations, DFT Calculations, and Molecular Docking Studies of Novel 2-(Substituted-Aryloxymethyl)-5-(Pyridin-4-yl)-1, 3, 4-Oxadiazoles: Highly Potential InhA and Cytochrome c Peroxidase Inhibitors DOI

Madhura Datar,

Ramagopal Dhanwad,

Mohammad Javeed

et al.

Polycyclic aromatic compounds, Journal Year: 2023, Volume and Issue: 44(1), P. 473 - 487

Published: Feb. 15, 2023

We report derivatives of 2,5-disubstituted-1,3,4-oxadiazole as powerful anti-TB and antioxidant compounds. Using substituted aryloxy acetic acids (2a–f) isoniazid (3) in the presence phosphorus oxychloride, a series new 2-(substituted-aryloxymethyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoles (4a–f) are synthesized. IR, 1H NMR, mass spectral data were used to physically spectroscopically describe synthesized molecules. Density Functional Theory (DFT) calculations performed at DFT/B3LYP level using 6-31 G++ (d, p) reproduce structure geometry. The non-linear visual characteristic compounds is determined by first-order hyperpolarizability calculation. To analyze charge transfer interface between structures, HOMO LUMO investigations used. vitro activity was carried out. compound 4d exhibited excellent with MIC value 3.12 µg/ml. 4b 4c showed promising concentration 10 µg/ml inhibition rates 68.36% 69.26% respectively. Furthermore, docking studies for newly molecules out Auto dock software proteins InhA (4TZK) Cytochrome c peroxidase (2X08). All strong binding affinity docked proteins.

Language: Английский

Citations

20
Investigating the molecular interactions of 11-substituted-1-(4-chlorophenyl)-8H-indolo[3,2-c][1,2,4]triazolo[3,4-a]isoquinolines for Antimicrobial Potential: Synthesis, Spectral, In vitro and In silico study interpretations DOI

B. T. Sridhar,

Mohammad Javeed,

Prashantha Karunakar

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1312, P. 138617 - 138617

Published: May 12, 2024

Language: Английский

Citations

8
Investigation of embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, spectral analysis, DFT calculations and molecular docking studies DOI

Basavarajaiah Suliphuldevara Mathada,

N. Jeelan Basha, Prashantha Karunakar

et al.

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1273, P. 134356 - 134356

Published: Oct. 17, 2022

Language: Английский

Citations

28
The Benzoxazole Heterocycle: A Comprehensive Review of the Most Recent Medicinal Chemistry Developments of Antiproliferative, Brain-Penetrant, and Anti-inflammatory Agents DOI
Simona Di Martino, Maria De Rosa

Topics in Current Chemistry, Journal Year: 2024, Volume and Issue: 382(4)

Published: Oct. 21, 2024

Language: Английский

Citations

4
Overexpression of lncRNA TINCR inhibits cutaneous squamous cell carcinoma cells through promotes methylation of Myc and TERC genes DOI Creative Commons
Liang Wang, Yu Wang, Lei Xu

et al.

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: March 12, 2025

Long non-coding RNA (lncRNA) TINCR has been shown to play a crucial regulatory role in various tumors. However, its specific mechanism of action cutaneous squamous cell carcinoma (CSCC) remains unclear. This study aimed explore the lncRNA CSCC. We utilized overexpression techniques effects on CSCC cells. Methylation-specific PCR (MSP) and immunoprecipitation (RIP) assays were used assess impact methylation promoter regions Myc TERC genes, interaction with DNA methyltransferase 1 (DNMT1). The results showed that significantly promoted (N-MYC, L-MYC, c-MYC) inhibiting proliferation, migration, invasion MSP RIP experiments further confirmed binds DNMT1, enhancing levels genes. These findings suggest may serve as potential therapeutic target for by regulating key oncogenes. provide new insights into molecular mechanisms highlight targeting TINCR.

Language: Английский

Citations

0
Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation DOI
N. Jeelan Basha,

Raju Mohan

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(10)

Published: March 6, 2024

Abstract Transcription factor p53, also known as tumor suppressor protein. Encoded by the TP53 gene, guardian of genome p53 regulates many gene pathways. Nevertheless, molecular mechanisms functioning have been for a few decades, and exact role in cancer therapy is unclear. Also, comprehensive literature on heterocycles p53‐MDM2 protein‐protein interaction inhibitors limited. This review covers mechanism its inhibition heterocyclic small molecules. We hope present study will help to develop anticancer drugs that induce apoptosis cells.

Language: Английский

Citations

3