Bioactive Tryptophan-Based Copper Complex with Auxiliary β-Carboline Spectacle Potential on Human Breast Cancer Cells: In Vitro and In Vivo Studies.

Walaa Alharbi,Shazia Parveen,Ibrahim M Alhazza,Ibtisam I Bin Sharfan,Iftekhar Hassan,Rais Ahmad Khan,Ali Alsalme,Khadijah H Alharbi,Hossam Ebaid

doi:10.3390/molecules26061606

Abstract

Biocompatible tryptophan-derived copper (1) and zinc (2) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC50 value of 7.8 ± 0.4 μM compared to 2 (less active, IC50 ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1.

Highlights

IntroductionCurrent cancer chemotherapies often fail to improve patient mortality and morbidity due to severe adverse effects on normal tissues
The synthesis involved the in situ reaction of tryptophane and salicylaldehyde in the equimolar ratio in methanol to get the characteristic yellow colored solution of Schiff base
The results revealed in MCF7 cells treating with complex 1 decreases the level of GSH in a concentration dependent manner

Summary

Introduction

Current cancer chemotherapies often fail to improve patient mortality and morbidity due to severe adverse effects on normal tissues. In 1978, Food and Drug Administration approved cisplatin as an anticancer drug for clinical use. Cisplatin and its analogues are very useful chemotherapeutic agents in treating testicular and ovarian cancers [2]. The modern use of transition metal complexes as chemotherapeutic agents dates back to the serendipitous cisplatin discovery by Rosenberg et al in 1965 [1,3]. Despite the success of cisplatin and platinum-based drugs, they still stumble upon much resistance, undesirable non-cancer cell toxicity, and limited activity [4,5]. The market is always accessible for new advantageous metalbased drugs that offer better viability, such as oral administration, which might diminish severe side-effects and clinic costs.

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