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

и другие.

Опубликована: Авг. 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

Язык: Английский

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

Raju Mohan

ChemistrySelect, Год журнала: 2024, Номер 9(10)

Опубликована: Март 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.

Язык: Английский

Процитировано

3
Synthesis of Pharmacologically Potent Benzimidazole Analogs DOI

Jeelan Basha Nagenahalli,

Prashanth Reddiyappa,

Akshay K Thammaiah

и другие.

Polycyclic aromatic compounds, Год журнала: 2024, Номер unknown, С. 1 - 17

Опубликована: Авг. 13, 2024

Язык: Английский

Процитировано

3
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

и другие.

Archives of Dermatological Research, Год журнала: 2025, Номер 317(1)

Опубликована: Март 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Chemistry, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 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) .

Язык: Английский

Процитировано

0
Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways DOI
N. Jeelan Basha,

T. L. Chandana

ChemistrySelect, Год журнала: 2023, Номер 8(19)

Опубликована: Май 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.

Язык: Английский

Процитировано

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

и другие.

eLife, Год журнала: 2024, Номер 12

Опубликована: Апрель 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

Язык: Английский

Процитировано

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 Creative Commons
Atikul Islam,

Yu-Chun Chang,

Xiao-Chi Chen

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Авг. 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

Язык: Английский

Процитировано

2
Epigenetic biomarkers DOI

Arnold Bhebhe,

Shabana S. Meyering,

Sabita N. Saldanha

и другие.

Elsevier eBooks, Год журнала: 2023, Номер unknown, С. 207 - 257

Опубликована: Окт. 20, 2023

Язык: Английский

Процитировано

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

и другие.

Опубликована: Фев. 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

Язык: Английский

Процитировано

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

и другие.

Опубликована: Фев. 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

Язык: Английский

Процитировано

0