LAPSE:2023.0160
Published Article
LAPSE:2023.0160
Novel Semisynthetic Betulinic Acid−Triazole Hybrids with In Vitro Antiproliferative Potential
February 17, 2023
Betulinic acid, BA, is a lupane derivative that has caught the interest of researchers due to the wide variety of pharmacological properties it exhibits towards tumor cells. Because of their prospective increased anti−proliferative efficacy and improved pharmacological profile, BA derivatives continue to be described in the scientific literature. The current work was conducted in order to determine the antiproliferative activity, under an in vitro environment of the newly developed 1,2,4−triazole derivatives of BA. The compounds and their reaction intermediates were tested on three cancer cell lines, namely RPMI−7951 human malignant melanoma, HT−29 colorectal adenocarcinoma, A549 lung carcinoma, and healthy cell line (HaCaT human keratinocytes). BA−triazole derivatives 4a and 4b revealed lower IC50 values in almost all cases when compared to their precursors, exhibiting the highest cytotoxicity against the RPMI−7951 cell line (IC50: 18.8 μM for 4a and 20.7 μM for 4b). Further biological assessment of these compounds executed on the most affected cell line revealed a mitochondrial level induced apoptotic mechanism where both compounds inhibited mitochondrial respiration in RPMI−7951 cells. Furthermore, the triazole−BA derivatives caused a significant decrease of the anti−apoptotic Bcl−2 gene expression, while increasing the pro−apoptotic BAX gene’s expression.
Record ID
Keywords
antiproliferative, betulinic acid−triazole derivatives, colorectal adenocarcinoma, cytotoxicity, lung carcinoma, melanoma
Subject
Suggested Citation
Nistor G, Mioc A, Mioc M, Balan-Porcarasu M, Ghiulai R, Racoviceanu R, Avram ?, Prodea A, Semenescu A, Milan A, Dehelean C, Șoica C. Novel Semisynthetic Betulinic Acid−Triazole Hybrids with In Vitro Antiproliferative Potential. (2023). LAPSE:2023.0160
Author Affiliations
Nistor G: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes
Mioc A: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Anatomy, Physiology, Pathophysiology, Faculty of Pharmacy, Victor Babes [ORCID]
Mioc M: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes
Balan-Porcarasu M: Institute of Macromolecular Chemistry ‘Petru Poni’, 700487 Iasi, Romania [ORCID]
Ghiulai R: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Pharmacology−Pharmacotherapy, Victor Babes University of Medicine and
Racoviceanu R: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Avram ?: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Deparment of Pharmacognosy, Faculty of Pharmacy, Victor Babes University of Medicine a [ORCID]
Prodea A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Semenescu A: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Toxicology, Faculty of Pharmacy, “Victor Babes” University of Medici [ORCID]
Milan A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Dehelean C: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Toxicology, Faculty of Pharmacy, “Victor Babes” University of Medici
Șoica C: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Pharmacology−Pharmacotherapy, Victor Babes University of Medicine and
Mioc A: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Anatomy, Physiology, Pathophysiology, Faculty of Pharmacy, Victor Babes [ORCID]
Mioc M: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes
Balan-Porcarasu M: Institute of Macromolecular Chemistry ‘Petru Poni’, 700487 Iasi, Romania [ORCID]
Ghiulai R: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Pharmacology−Pharmacotherapy, Victor Babes University of Medicine and
Racoviceanu R: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Avram ?: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Deparment of Pharmacognosy, Faculty of Pharmacy, Victor Babes University of Medicine a [ORCID]
Prodea A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Semenescu A: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Toxicology, Faculty of Pharmacy, “Victor Babes” University of Medici [ORCID]
Milan A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes [ORCID]
Dehelean C: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Toxicology, Faculty of Pharmacy, “Victor Babes” University of Medici
Șoica C: Research Centre for Pharmaco−Toxicological Evaluation, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania; Department of Pharmacology−Pharmacotherapy, Victor Babes University of Medicine and
Journal Name
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Volume
11
Issue
1
First Page
101
Year
2022
Publication Date
2022-12-29
Published Version
ISSN
2227-9717
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PII: pr11010101, Publication Type: Journal Article
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LAPSE:2023.0160
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doi:10.3390/pr11010101
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Feb 17, 2023
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