TY - JOUR
T1 - β-Carboline copper complex as a potential mitochondrial-targeted anticancer chemotherapeutic agent
T2 - Favorable attenuation of human breast cancer MCF7 cells via apoptosis
AU - Khan, Rais Ahmad
AU - Khan, Mohammad Rashid
AU - Usman, Mohammad
AU - Sayeed, Fatima
AU - Alghamdi, Huda A.
AU - Alrumman, Sulaiman
AU - Alharbi, Walaa
AU - Farshori, Nida N.
AU - Al-Oqail, Mai M.
AU - Siddiqui, Mohd Rafiq
AU - Khanjer, Maymonah Abu
AU - Alsalme, Ali
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2020/8
Y1 - 2020/8
N2 - The development of preferentially selective cancer chemotherapeutics is a new trend in drug research. Thus, we designed and synthesized novel ternary complexes, [Cu(tryp)(Hnor)2(DMSO)]NO3 (1) and [Zn(tryp)(Hnor)2(DMSO)]NO3 (2) (tryp = DL-Tryptophane; Hnor = Norharmane, β-carboline; DMSO = Dimethyl sulfoxide), characterized with elemental analysis, FTIR, UV–vis, FL, NMR, ESI-MS, and molar conductivity. Furthermore, the TD-DFT studies with UV–vis and FTIR validated the proposed structures of 1 and 2. Moreover, we evaluated the HOMO-LUMO energy gap and found that 1 has a smaller energy gap than 2. Then, 1 and 2 were assessed for anticancer chemotherapeutic potential against cancer cell lines MCF7 (human breast cancer) and HepG2 (human liver hepatocellular carcinoma) as well as the non-tumorigenic HEK293 (human embryonic kidney) cells. The MTT assay illustrated the preferentially cytotoxic behavior of 1 when compared with that of 2 and cisplatin (standard drug) against MCF7 cells. Moreover, 1 was exposed to MCF7 cells, and the results indicated the arrest of the G2/M phases, which followed the apoptotic pathway predominantly. Generation of ROS, GSH depletion, and elevation in LPO validated the redox changes prompted by 1. These studies establish the great potential of 1 as a candidate for anticancer therapeutics.
AB - The development of preferentially selective cancer chemotherapeutics is a new trend in drug research. Thus, we designed and synthesized novel ternary complexes, [Cu(tryp)(Hnor)2(DMSO)]NO3 (1) and [Zn(tryp)(Hnor)2(DMSO)]NO3 (2) (tryp = DL-Tryptophane; Hnor = Norharmane, β-carboline; DMSO = Dimethyl sulfoxide), characterized with elemental analysis, FTIR, UV–vis, FL, NMR, ESI-MS, and molar conductivity. Furthermore, the TD-DFT studies with UV–vis and FTIR validated the proposed structures of 1 and 2. Moreover, we evaluated the HOMO-LUMO energy gap and found that 1 has a smaller energy gap than 2. Then, 1 and 2 were assessed for anticancer chemotherapeutic potential against cancer cell lines MCF7 (human breast cancer) and HepG2 (human liver hepatocellular carcinoma) as well as the non-tumorigenic HEK293 (human embryonic kidney) cells. The MTT assay illustrated the preferentially cytotoxic behavior of 1 when compared with that of 2 and cisplatin (standard drug) against MCF7 cells. Moreover, 1 was exposed to MCF7 cells, and the results indicated the arrest of the G2/M phases, which followed the apoptotic pathway predominantly. Generation of ROS, GSH depletion, and elevation in LPO validated the redox changes prompted by 1. These studies establish the great potential of 1 as a candidate for anticancer therapeutics.
KW - Anticancer
KW - Apotosis
KW - Cell cycle
KW - Computational chemistry
KW - Copper complex
KW - MCF7
UR - https://www.scopus.com/pages/publications/85084656725
U2 - 10.1016/j.sjbs.2020.05.001
DO - 10.1016/j.sjbs.2020.05.001
M3 - Article
AN - SCOPUS:85084656725
SN - 1319-562X
VL - 27
SP - 2164
EP - 2173
JO - Saudi Journal of Biological Sciences
JF - Saudi Journal of Biological Sciences
IS - 8
ER -