2. Academic Validation
  3. A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells

A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells

  • Eur J Med Chem. 2016 Jan 27:108:104-116. doi: 10.1016/j.ejmech.2015.11.018.
Imran Khan 1,  Santosh K Guru 2,  Santosh K Rath 3,  Praveen K Chinthakindi 1,  Buddh Singh 1,  Surrinder Koul 1,  Shashi Bhushan 4,  Payare L Sangwan 5
Affiliations

Affiliations

  • 1 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 2 Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 3 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
  • 4 Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: sbhushan@iiim.ac.in.
  • 5 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India. Electronic address: plsangwan@iiim.ac.in.
PMID: 26629862 DOI: 10.1016/j.ejmech.2015.11.018
Abstract

In an attempt to arrive at more potent cytotoxic agent than the bioactive natural product betulinic acid, influence of small structural modifications of its 1, 2, 3 triazole derivatives tethered at C-28 and both C3, C-28 using Click Chemistry approach has been studied. The chemically characterized triazoles have been screened for in vitro cytotoxicity against four human Cancer cell lines HL-60, MiaPaCa-2, PC-3 and A549 which has allowed to identify triazole derivative 28{1N (4-fluoro phenyl)-1H-1, 2, 3-triazol-4-yl} methyloxy betulinic ester having better potency profile than the parent compound with IC50 values in the range of 5-7 μM. It caused disruption of mitochondrial membrane potential, rendered Bcl-2 cleavage, Bax translocation and decrease Bcl-2/Bax ratio. These events are accompanied by activation of caspases -9, -3, which cleave the PARP-1. It also induces Caspase-8, which is involved in extrinsic apoptotic pathway. Therefore, it induces Apoptosis through both intrinsic and extrinsic pathways in human leukemia HL-60 cells.

Keywords

Apoptosis; Betulinic acid; Click chemistry; Human leukemia; Triazole derivative.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z