2. Academic Validation
  3. Design, synthesis, mechanistic and histopathological studies of small-molecules of novel indole-2-carboxamides and pyrazino[1,2-a]indol-1(2H)-ones as potential anticancer agents effecting the reactive oxygen species production

Design, synthesis, mechanistic and histopathological studies of small-molecules of novel indole-2-carboxamides and pyrazino[1,2-a]indol-1(2H)-ones as potential anticancer agents effecting the reactive oxygen species production

  • Eur J Med Chem. 2018 Feb 25:146:260-273. doi: 10.1016/j.ejmech.2018.01.042.
Bahaa G M Youssif 1,  Mostafa H Abdelrahman 2,  Ahmed H Abdelazeem 3,  Mohamed A Abdelgawad 4,  Hussein M Ibrahim 5,  Ola I A Salem 6,  Mamdouh F A Mohamed 7,  Laurent Treambleau 8,  Syed Nasir Abbas Bukhari 9
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka, 2014, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt. Electronic address: bgyoussif@ju.edu.sa.
  • 2 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt.
  • 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt; College of Medicine, Al-Rayyan Colleges, Al Madinah Al Munawarah, 41411, Saudi Arabia.
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka, 2014, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt.
  • 5 Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Aljouf University, Aljouf, Sakaka, 2014, Saudi Arabia.
  • 6 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
  • 7 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524, Sohag, Egypt.
  • 8 School of Natural and Computing Sciences, University of Aberdeen, Meston Building, Aberdeen, AB243UE, Ireland.
  • 9 Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Aljouf, Sakaka, 2014, Saudi Arabia. Electronic address: snab_hussaini@yahoo.com.
PMID: 29407956 DOI: 10.1016/j.ejmech.2018.01.042
Abstract

A series of novel compounds carrying pyrazino[1,2-a]indol-1(2H)-one scaffold (5a-g) and their reaction intermediates, indole-2-carboxamides, (3a-g) were synthesized and evaluated for their ability to inhibit Reactive Oxygen Species (ROS) generation, antioxidant activity and Anticancer activity against a panel of Cancer cell lines using MTT assay. The results showed that these compounds can inhibit ROS generation during the metabolic phase of phagocytosis in a dose-dependent manner where compounds 5d and 5e were the most potent samples with higher inhibitory activities (IC50 values 3.3 and 1.4 μM, respectively) than that of the reference acetylsalicylic acid (IC50 = 9.7 μM). Results for the determination of potential antioxidant properties of the synthesized compounds showed that compounds 5d and 5e containing pyrazino[1,2-a]indol-1-one backbone were the most acive and even comparable to Trolox. Compounds 3d-f and 5d-f with the least IC50 values in MTT assay were tested against three known Anticancer targets EGFR, BRaf and Tubulin. Histopathological and immunohistochemical study were performed to determine the consequence of exposure to chronic low dose of chlorpyrifos on the testis of male mice and results revealed that these effects can be ameliorated by co-treatment with the most active antioxidant compounds 5d and 5e. Finally, molecular docking studies were performed to explore the binding mode of the most active compounds against EGFR and BRaf kinases.

Keywords

Anti-cancer; Anti-oxidant; BRAF; Docking; EGFR; Indole-2-carboxamides; Pyrazino[1,2-a]indole.

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