LAPSE:2024.1110
Published Article
LAPSE:2024.1110
Novel Betulin-1,2,4-Triazole Derivatives Promote In Vitro Dose-Dependent Anticancer Cytotoxicity
June 21, 2024
Abstract
Betulin is a birch bark-derived lupane-type pentacyclic triterpene with a wide spectrum of biological activities. Given their enhanced antiproliferative potential and enhanced pharmacological profile, betulin derivatives are continuously investigated in scientific studies. The objective of the current study was to in vitro assess the antiproliferative properties of novel synthesized 1,2,4-triazole derivatives of diacetyl betulin. The compounds were investigated using three cancer cell lines: A375 (melanoma), MCF-7 (breast cancer), HT-29 (colorectal cancer), and HaCaT (human keratinocytes). Bet-TZ1 had the lowest recorded IC50 values (ranging from 22.41 to 46.92 μM after 48 h of exposure) than its precursor and other tested compounds in every scenario, with the highest cytotoxicity against the A375 cell line. Bet-TZ3 demonstrated comparable cytotoxicity to the previously mentioned compound, with an IC50 of 34.34 μM against A375. Both compounds caused apoptosis in tested cells, by inducing specific nuclear morphological changes and by increasing the expression of caspase 9, indicating significant cytotoxicity, which was consistent with the literature and viability evaluation. Bet-TZ1 and Bet-TZ3 inhibit cancer cell migration, with the former having a stronger effect than the latter. The HET−CAM test indicated that all compounds have no irritative potential, suggesting that they can be used locally.
Betulin is a birch bark-derived lupane-type pentacyclic triterpene with a wide spectrum of biological activities. Given their enhanced antiproliferative potential and enhanced pharmacological profile, betulin derivatives are continuously investigated in scientific studies. The objective of the current study was to in vitro assess the antiproliferative properties of novel synthesized 1,2,4-triazole derivatives of diacetyl betulin. The compounds were investigated using three cancer cell lines: A375 (melanoma), MCF-7 (breast cancer), HT-29 (colorectal cancer), and HaCaT (human keratinocytes). Bet-TZ1 had the lowest recorded IC50 values (ranging from 22.41 to 46.92 μM after 48 h of exposure) than its precursor and other tested compounds in every scenario, with the highest cytotoxicity against the A375 cell line. Bet-TZ3 demonstrated comparable cytotoxicity to the previously mentioned compound, with an IC50 of 34.34 μM against A375. Both compounds caused apoptosis in tested cells, by inducing specific nuclear morphological changes and by increasing the expression of caspase 9, indicating significant cytotoxicity, which was consistent with the literature and viability evaluation. Bet-TZ1 and Bet-TZ3 inhibit cancer cell migration, with the former having a stronger effect than the latter. The HET−CAM test indicated that all compounds have no irritative potential, suggesting that they can be used locally.
Record ID
Keywords
betulin, breast cancer, colorectal cancer, cytotoxicity, melanoma, triazole derivatives
Subject
Suggested Citation
Prodea A, Milan A, Mioc M, Mioc A, Oprean C, Racoviceanu R, Negrea-Ghiulai R, Mardale G, Avram Ș, Balan-Porcărașu M, Rotunjanu S, Trandafirescu C, Şoica I, Șoica C. Novel Betulin-1,2,4-Triazole Derivatives Promote In Vitro Dose-Dependent Anticancer Cytotoxicity. (2024). LAPSE:2024.1110
Author Affiliations
Prodea A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic [ORCID]
Milan A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic [ORCID]
Mioc M: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic
Mioc A: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Oprean C: Department of Drug Analysis, Environmental Chemistry, Hygiene and Nutrition, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Chemistry and Toxicology, OncoGen Ce
Racoviceanu R: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic [ORCID]
Negrea-Ghiulai R: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Mardale G: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Avram Ș: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacognosy, Faculty of Pharmacy, Victor Babes University of Medicine and Pha [ORCID]
Balan-Porcărașu M: Institute of Macromolecular Chemistry ‘Petru Poni’, 700487 Iasi, Romania [ORCID]
Rotunjanu S: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Trandafirescu C: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic
Şoica I: Medical School, University College London, 74 Huntley St., London WC1E 6DE, UK
Șoica C: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Milan A: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic [ORCID]
Mioc M: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic
Mioc A: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Oprean C: Department of Drug Analysis, Environmental Chemistry, Hygiene and Nutrition, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Chemistry and Toxicology, OncoGen Ce
Racoviceanu R: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic [ORCID]
Negrea-Ghiulai R: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Mardale G: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Avram Ș: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacognosy, Faculty of Pharmacy, Victor Babes University of Medicine and Pha [ORCID]
Balan-Porcărașu M: Institute of Macromolecular Chemistry ‘Petru Poni’, 700487 Iasi, Romania [ORCID]
Rotunjanu S: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Trandafirescu C: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medic
Şoica I: Medical School, University College London, 74 Huntley St., London WC1E 6DE, UK
Șoica C: Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timișoara, Romania; Department of Pharmacology-Pharmacotherapy, Faculty of Pharmacy, Victor Babes University of M
Journal Name
Processes
Volume
12
Issue
1
First Page
24
Year
2023
Publication Date
2023-12-21
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr12010024, Publication Type: Journal Article
Record Map
Published Article
LAPSE:2024.1110
This Record
External Link
https://doi.org/10.3390/pr12010024
Publisher Version
Download
Meta
Record Statistics
Record Views
197
Version History
[v1] (Original Submission)
Jun 21, 2024
Verified by curator on
Jun 21, 2024
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2024.1110
Record Owner
Auto Uploader for LAPSE
Links to Related Works