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

Insights into Novel Isoniazide Encompassing triazolo[4,3-b][1,2,4]triazoles as Anti-TB, Antioxidant and Antidiabetic agents: A Spectral analysis, DFT calculations, ADME, In vitro, and in silico Molecular Modeling Studies DOI

Parveen Rajesab,

Basavarajaiah Suliphuldevara Mathada,

Vidya Niranjan

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141876 - 141876

Published: Feb. 1, 2025

Language: Английский

Citations

0
Design, Synthesis, and In Vitro and In Silico Biological Exploration of Novel Pyridine‐Embedded 1,3,4‐Oxadiazole Hybrids as Potential Antimicrobial Agents DOI Creative Commons

K. N. Shivakumara,

S. M. Basavarajaiah,

Nagesh Gunavanthrao Yernale

et al.

Journal of Chemistry, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Antibiotic resistance represents a significant public health challenge in the current century. The β‐lactam antibiotics, together with carbapenems, are inactivated by zinc‐dependent bacterial enzymes called metallo‐β‐lactamases (MBLs). Presently there no clinically permitted MBL inhibitors, and to produce such drugs, it is indispensable comprehend their inhibitory action. We investigated an efficient synthesis of pyridine‐embedded 1,3,4‐oxadiazole hybrids (3a-c) antimicrobial activity against different microbial strains. compounds were characterized spectral techniques (viz., IR, NMR, mass). vitro antibacterial antifungal was also performed; displayed excellent activity. silico docking studies evaluated proteins New Delhi Metallo-Beta-lactamase-1 (NDM‐1) Mycobacterium tuberculosis enoyl reductase (INHA). All demonstrated binding affinity for docked proteins. Additionally, molecular dynamics disclosed (4a-c) .

Language: Английский

Citations

0
Synthesis of Pharmacologically Potent Benzimidazole Analogs DOI

Jeelan Basha Nagenahalli,

Prashanth Reddiyappa,

Akshay K Thammaiah

et al.

Polycyclic aromatic compounds, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Aug. 13, 2024

Language: Английский

Citations

2
Investigation of Novel 2‐(Chloromethyl)‐5‐(3, 5‐Disubstituted‐1H‐Indol‐2‐yl)‐1,3,4‐Oxadiazole Derivatives as In Vitro, and In Silico Bioactivity Potential: Anti‐inflammatory, Anti‐TB and Antioxidant Activities Study DOI

K. Harish Kumar,

B. T. Sridhar,

Prashantha Karunakar

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(33)

Published: Sept. 4, 2024

Abstract A series of novel 2‐(chloromethyl)‐5‐(3, 5‐disubstituted‐1 H ‐indol‐2‐yl)‐1,3,4‐oxadiazole ( 3 a – h ) derivatives have been synthesized as potential COX inhibitors, anti‐TB, and anti‐oxidant activities. The structures were confirmed by IR, NMR 1 13 C) mass spectral techniques. physicochemical properties, ADME, drug‐likeness profile for the compounds evaluated SwissADME. Based on our interest in indole chemistry SAR study, foresaid examined vitro inhibitory activity, antioxidant ADME studies disclosed newly compounds. , b c recognized outstanding COX‐II inhibitions with IC 50 values 0.28, 0.24, 0.45 μM compared to standard drugs. ,and showed anti‐TB activity MIC value 0.78 μg/mL. attested at 10 μg/ml rate inhibition 66.52 %, 68.25 65.95 % respectively. Finally, molecular docking carried out cyclooxygenase‐2 PDB ID: 6COX ), M. tuberculosis enoyl reductase (INHA) complexed 1‐cyclohexyl‐ N ‐(3,5‐dichlorophenyl)‐5‐oxopyrrolidine‐3‐carboxamide 4TZK cytochrome peroxidase 2X08 all derivatives. selected taken their dynamic studies.

Language: Английский

Citations

2
Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways DOI
N. Jeelan Basha,

T. L. Chandana

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(19)

Published: May 16, 2023

Abstract To date, viruses are known to cause chronic acute pathogenesis. Nevertheless, antiviral drugs have been for their medicinal applications the last few decades treat infections caused by these pathogens. Despite advancements in field of vaccination and drugs, there is a need molecule that can eradicate or control viral infection without getting resistance from pathogens will be real challenge. This review covers possible ways with pyrimidine its mimics compared drugs. A comprehensive study report accomplished synthetic routes analogs target‐specific potential. The present article literature 2018 2022.

Language: Английский

Citations

6
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 Creative Commons
Atikul Islam,

Yu-Chun Chang,

Xiao-Chi Chen

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: April 3, 2024

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 (CETSA) and molecular docking simulations identify validate water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged targeted with sirtuin-1 (SIRT1) p53-functional SAS p53-mutated HSC-3 oral cancer cells. We further addressed outcome SIRT1 inhibition these compounds found that, addition SIRT1, 4-dmH preferentially a tumor-associated NADH oxidase (tNOX, ENOX2). direct binding tNOX decreased oxidation NAD + diminished -dependent deacetylase activity, ultimately inducing apoptosis significant cytotoxicity both cell types, as opposed parental heliomycin-induced autophagy. 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, our vitro vivo findings suggest multifaceted properties enable it offer superior antitumor value heliomycin, indicated functions through targeting tNOX-NAD -SIRT1 axis induce

Language: Английский

Citations

1
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 Creative Commons
Atikul Islam,

Yu-Chun Chang,

Xiao-Chi Chen

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

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 (CETSA) and molecular docking simulations identify validate water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged targeted with sirtuin-1 (SIRT1) p53-functional SAS p53-mutated HSC-3 oral cancer cells. We further addressed outcome SIRT1 inhibition these compounds found that, addition SIRT1, 4-dmH preferentially a tumor-associated NADH oxidase (tNOX, ENOX2). direct binding tNOX decreased oxidation NAD + diminished -dependent deacetylase activity, ultimately inducing apoptosis significant cytotoxicity both cell types, as opposed parental heliomycin-induced autophagy. 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, our vitro vivo findings suggest multifaceted properties enable it offer superior antitumor value heliomycin, indicated functions through targeting tNOX-NAD -SIRT1 axis induce

Language: Английский

Citations

2
Epigenetic biomarkers DOI

Arnold Bhebhe,

Shabana S. Meyering,

Sabita N. Saldanha

et al.

Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 207 - 257

Published: Oct. 20, 2023

Language: Английский

Citations

2
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,

Yu-Chun Chang,

Xiao-Chi Chen

et al.

Published: Feb. 20, 2024

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 (CETSA) and molecular docking simulations identify validate water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged targeted with sirtuin-1 (SIRT1) p53-functional SAS p53-mutated HSC-3 oral cancer cells. We further addressed outcome SIRT1 inhibition these compounds found that, addition SIRT1, 4-dmH preferentially a tumor-associated NADH oxidase (tNOX, ENOX2). direct binding tNOX decreased oxidation NAD + diminished -dependent deacetylase activity, ultimately inducing apoptosis significant cytotoxicity both cell types, as opposed parental heliomycin-induced autophagy. 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, our vitro vivo findings suggest multifaceted properties enable it offer superior antitumor value heliomycin, indicated functions through targeting tNOX-NAD -SIRT1 axis induce

Language: Английский

Citations

0
Author Response: 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,

Yu-Chun Chang,

Xiao-Chi Chen

et al.

Published: Feb. 20, 2024

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 (CETSA) and molecular docking simulations identify validate water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged targeted with sirtuin-1 (SIRT1) p53-functional SAS p53-mutated HSC-3 oral cancer cells. We further addressed outcome SIRT1 inhibition these compounds found that, addition SIRT1, 4-dmH preferentially a tumor-associated NADH oxidase (tNOX, ENOX2). direct binding tNOX decreased oxidation NAD+ diminished NAD+-dependent deacetylase activity, ultimately inducing apoptosis significant cytotoxicity both cell types, as opposed parental heliomycin-induced autophagy. 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, our vitro vivo findings suggest multifaceted properties enable it offer superior antitumor value heliomycin, indicated functions through targeting tNOX-NAD+-SIRT1 axis induce

Language: Английский

Citations

0