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

TY - JOUR

T1 - Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents

AU - Majeed, Rabiya

AU - Sangwan, Payare L

AU - Chinthakindi, Praveen K

AU - Khan, Imran

AU - Dangroo, Nisar A

AU - Thota, Niranjan

AU - Hamid, Abid

AU - Sharma, Parduman R

AU - Saxena, Ajit K

AU - Koul, Surrinder

N1 - Copyright © 2013 Elsevier Masson SAS. All rights reserved.

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cell Survival

KW - DNA Fragmentation

KW - Dose-Response Relationship, Drug

KW - Electrophoresis, Agar Gel

KW - HL-60 Cells

KW - Humans

KW - Inhibitory Concentration 50

KW - MCF-7 Cells

KW - Membrane Potential, Mitochondrial

KW - Models, Chemical

KW - Molecular Structure

KW - Structure-Activity Relationship

KW - Triazoles

KW - Triterpenes

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejmech.2013.03.028

DO - 10.1016/j.ejmech.2013.03.028

M3 - Journal article

C2 - 23584541

SN - 0223-5234

VL - 63

SP - 782

EP - 792

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -