Design, Synthesis, and Antiproliferative Activity of Novel Neocryptolepine–Rhodanine Hybrids

Abstract

A series of novel neocryptolePine–rhodanine hybrids (9a,b, 11a–d, 14, and 16a,b) have been synthesized by combining neocryptolePine core 5 modified at the C-11 position with rhodanine condensed with the appropriate aryl/hetero aryl aldehydes. Based on these findings, the structures of the hybrids were confirmed by spectral analyses. By employing the MTT assay, all hybrids were tested for their in vitro antiproliferative activity against two cancer cell lines, including MDA-MB-231 (human breast) and HepG-2 (hepatocellular carcinoma). Interestingly, the IC50 values of all hybrids except 9b and 11c showed activity comparable to the standard anticancer drug, 5-fluorouracil, against HepG-2 cancer cells. Furthermore, the cytotoxicity of all the synthesized hybrids was investigated on a normal skin human cell line (BJ-1), and the results showed that these compounds had no significant cytotoxicity toward these healthy cells at the highest concentration used in this study. This study also indicated that the active hybrids exert their cytotoxic activity via the induction of apoptosis. A molecular docking study was used to shed light on the molecular mechanism of their anticancer activity. The docking results revealed that the hybrids exert their mode of action through DNA intercalation. Furthermore, in silico assessment for pharmacokinetic properties was performed on the most potent compounds, which revealed candidates with good bioavailability, high tolerability with cell membranes, and positive drug-likeness values.

Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model

“…The Commercially available starting materials and solvents such as dimethyl formamide (DMF), and dimethyl sulfoxide (DMSO) were purchased from Sigma Aldrich and used as received without further purification. The key starting intermediate, 11-chloroneocryptolepine 1 was prepared according to our reported method [ 10 ]. Soluble starch was purchased from Doummar & Sons Co. Industrial City, Syria.…”

“…In last decades, nature is fruitful and active area for many pharmaceutical compounds encouraging researchers to discover and develop compounds to reach the best and optimum activity against several diseases [ 10 ].…”

“…Neocryptolepine I (5-methyl-5H-indolo[2,3-b] quinoline) and its region isomer cryptolepine II (5-methyl-5H-indolo[3,2-b]quinoline) presented in ( Scheme 1 ) have potent biological activity as anticancer, antimalarial and antimicrobial. Many structural modification and optimization were carried out to the lead core aiming to enhance and reach the best pharmaceutical properties for these alkaloids [ 10 ]. In addition, it was reported that upon in vitro inflammatory stimulation, cryptolepine has been demonstrated to reduce nitric oxide generation and nuclear factor-kappa B (NF-ĸB) DNA binding [ 12 ].…”

Polyrhodanine-based nanomaterials for biomedical applications: A review

“…Rhodanine and its derivatives have been widely studied as a potential anti-tumour agent due to its medical properties [ [97] , [98] , [99] ], however, PR has participated in a limited number of cancer-related research. A series of neocryptolepine–rhodanine hybrids was formed and tested as an anticancer drug [ 100 ]. The MTT assay showed that most of the formed hybrids had effective cytotoxicity on the tumour cell line hepatocellular carcinoma (HepG-2), similar to the standard drug 5-fluorouracil (5-FU).…”

“…Eggers et al studied the toxicity of rhodanine on kidney cells of monkeys, his results demonstrated that rhodanine had no toxic effect at a concentration of 150 μg/ml, but caused granulation of cells at a concentration of 200 μg/ml after a 4-day or longer exposure [ 119 ]. El-Bahnsawye et al evaluated a series of neocryptolepine (a natural plant extract) and rhodanine hybrids towards human breast (MDA-MB-231) and hepatocellular carcinoma (HepG-2) cancer cell lines [ 100 ]. In this research, they revealed that the tested hybrids showed strong selectivity for cancer cells over normal skin cell lines (BJ-1) at the maximum concentration.…”