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

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

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 137, С. 106598 - 106598

Опубликована: Май 9, 2023

Язык: Английский

Процитировано

27
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

и другие.

Journal of the Iranian Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Язык: Английский

Процитировано

2
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

и другие.

Journal of Molecular Structure, Год журнала: 2023, Номер 1287, С. 135685 - 135685

Опубликована: Апрель 29, 2023

Язык: Английский

Процитировано

23
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

и другие.

Polycyclic aromatic compounds, Год журнала: 2023, Номер 44(1), С. 473 - 487

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 42(4), С. 1751 - 1764

Опубликована: Апрель 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

Язык: Английский

Процитировано

22
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

и другие.

Journal of Molecular Structure, Год журнала: 2024, Номер 1312, С. 138617 - 138617

Опубликована: Май 12, 2024

Язык: Английский

Процитировано

9
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

и другие.

Journal of Molecular Structure, Год журнала: 2025, Номер unknown, С. 141876 - 141876

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
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

и другие.

Journal of Molecular Structure, Год журнала: 2022, Номер 1273, С. 134356 - 134356

Опубликована: Окт. 17, 2022

Язык: Английский

Процитировано

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, Год журнала: 2024, Номер 382(4)

Опубликована: Окт. 21, 2024

Язык: Английский

Процитировано

5
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

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(33)

Опубликована: Сен. 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.

Язык: Английский

Процитировано

4