Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone–Amino Acid Derivatives

Abstract

A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse L-and D-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from L-alanine, L-leucine, L-phenylalanine, and D-phenylalanine, were selected as promising compounds by their IC 50 ranging from 0.5 to 6.25 µM and also by their good selectivity indexes (≥2.24).

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

“…Recent studies from our research group (Bayrak et al, , ; Yildirim et al, ) and that of Ferreira (Dias et al ), Ryu (Ryu, Song, Lee, Hong, Yoon, & Kim, ; Ryu, Yoon, Song, Im, Kim, & Kim, ), Tandon (Tandon, Maurya, Kumar, Rashid, & Panda, ; Tandon et al, ), and Valderrama (Valderrama, Ibacache, Rodriguez, Theoduloz, & Benites, ; Valderrama, Leiva, Rodriguez, Theoduloz, & Schmeda‐Hirshmann, ) have shown that electrophilic character of 1,4‐quinones can undergo with neutral and/or anionic nucleophiles in different conditions in versatile reactions, thus leading to various biologically active (hetero)cyclic quinone structures for their pharmacological properties. In this regard, as a result of the immense value of quinone compounds in organic and medicinal chemistry, 1,4‐quinones have been studied for over a half‐century as an important class of building blocks and still continue to attract considerable attention due to the broad range of synthetic and medicinal applications (Bayrak et al, ; Johnson‐Ajinwo et al, ; Pingaew et al, ; Ravichandiran, Kannan, Ramasubbu, Muthusubramanian, & Samuel, ; Ravichandiran, Subramaniyan, et al, ; Tandon & Kumar, ; Valderrama et al, ; Wellington, ).…”

Screening for Selective Anticancer Activity of 65 Extracts of Plants Collected in Western Andalusia, Spain

“…A549 cells are epithelial cells and MRC-5 cells are fibroblastic cells. However, since normal epithelial cells are difficult to maintain and expand in culture, we selected this widely used normal cell line for our screening [11][12][13].…”

Antioxidant, anti-inflammatory and cytotoxic activities of the unsaponifiable fraction of extra virgin olive oil

“…Unsap exerts a low toxicity (CC 50 = 59 ± 3.9 µg/mL) on WI-38 human lung fibroblast normal cells (Figure 3e). However, the selective index (the ratio between IC 50 value for normal fibroblast cells and IC 50 value for cancer cells) towards HepG-2, A-549 and Panc-1 was 2.63, 1.94 and 3.01, respectively, indicating high selective toxicity (≥ 2) against those cancer cells as reported by Valderrama et al, (2016). Squalene has a chemopreventive effect against colon carcinogenesis (Rao et al, 1998).…”