2. Academic Validation
  3. Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity

Synthesis of 3-N-/O-/S-methyl-imidazo[1,2-a] pyridine derivatives for caspase-3 mediated apoptosis induced anticancer activity

  • Bioorg Chem. 2022 Aug;125:105882. doi: 10.1016/j.bioorg.2022.105882.
Davinder Singh 1,  Tenzen Yodun 2,  Gulshan Kumar 1,  Javeed Ahmad Tali 1,  Harshita Tiwari 1,  Jasvinder Singh 2,  Amit Nargotra 1,  Abhilash Samykutty 3,  Shashank Singh 4,  Ravi Shankar 5
Affiliations

Affiliations

  • 1 Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 2 Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 3 Stephenson Comprehensive Cancer Center, University of Oklahoma, Oklahoma City, OK 73104, USA.
  • 4 Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: sksingh@iiim.res.in.
  • 5 Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: rshankar@iiim.res.in.
PMID: 35660838 DOI: 10.1016/j.bioorg.2022.105882
Abstract

A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) Cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best Anticancer potential in all tested Cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon Cancer cells was achieved through the induction of Apoptosis via upregulation of the PTEN gene and downregulation of Akt pathway. Similarly, 5b treatment induced Caspase-3 cleavage which is a hallmark of Apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important Cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).

Keywords

Apoptosis; Caspase-3; Colon cancer; Imidazo[1,2-a]pyridine; Molecular docking studies; Morphological alteration.

Figures
Products
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