Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents

Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2013-05, Vol.63, p.782-792
Main Authors: Majeed, Rabiya, Sangwan, Payare L., Chinthakindi, Praveen K., Khan, Imran, Dangroo, Nisar A., Thota, Niranjan, Hamid, Abid, Sharma, Parduman R., Saxena, Ajit K., Koul, Surrinder
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Betulinic acid 1,2,3-trizole derivatives
Cell Line, Tumor
Cell Movement - drug effects
Cell Survival - drug effects
Click chemistry
Cytotoxicity
DNA fragmentation
DNA Fragmentation - drug effects
Dose-Response Relationship, Drug
Electrophoresis, Agar Gel
HL-60 Cells
Humans
Inhibitory Concentration 50
MCF-7 Cells
Membrane Potential, Mitochondrial - drug effects
Models, Chemical
Molecular Structure
Structure-Activity Relationship
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
Triterpenes - chemical synthesis
Triterpenes - chemistry
Triterpenes - pharmacology
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Summary:Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule. Two compounds i.e. 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (7) and 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (13) displayed impressive IC50 values (2.5 and 3.5 μM respectively) against leukemia cell line HL-60 (5–7-fold higher potency than betulinic acid). As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated. [Display omitted] Cytotoxic study of new betulinic acid triazoles showed two derivatives with 5 and 7-fold higher potency than betulinic acid against leukemia cancer cell line and found potential apoptotic agent. •Synthesis of 19 betulinic acid derivatives.•Several derivatives were active against various human cancer cell lines.•The molecules are apoptosis inducers.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.03.028