Search

Objective: The study was conducted to evaluate the in vitro and in silico anticancer activity of fluorinated podophyllotoxin derivatives. Methods: Microwave-assisted multicomponent reactions were carried out in an Anton Paar Microwave Synthetic Reactor Monowave 400 in order to synthesize fluorinated podophyllotoxin derivatives. These products were identified by spectral analysis and evaluated for their cytotoxicity against 4 types of human cancer cell lines (KB, HepG2, A549, and MCF7), as well as human embryonic kidney (Hek) 293 cells using MTT protocol. Molecular docking was conducted using 2 crystal structures of tubulin—colchicine (PDB ID: 4O2B) and topoisomerase II—etoposide (PDB ID: 3QX3) complexes. Results: Two potent cytotoxic fluorinated podophyllotoxin–naphthoquinone compounds were synthesized in good yields. They displayed high cytotoxic activity against all the tested cell lines, with IC50 values ranging from 0.58 to 3.17 µM. Notably, product 8a showed low toxicity against the Hek-293 cell line. Molecular docking results showed that products 8a and 8b participated in the same key interactions provided by etoposide with both topoisomerase and DNA chain domains. The binding energy values calculated for 8a and 8b are acceptable. Conclusion: This study revealed that products 8a and 8b exhibited promising in vitro and in silico anticancer activity and could be recognized as promising anticancer agents.

A series of novel naphthoquinone-fused podophyllotoxins containing fluoro and trifluoromethyl substituents were synthesized in a medium with good yields using two different synthetic approaches: microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, tetronic acid, fluorinated arylaldehydes, and ammonium acetate, and microwave-assisted three-component reactions of 2-amino-1,4-naphthoquinone, tetronic acid, and fluorinated arylaldehydes. The structures of all products were confirmed by spectral analysis. Together, cytotoxicity assessment of the products against four human cancer cell lines (human carcinoma [KB], human hepatocellular carcinoma [HepG2], lung cancer [A549], breast carcinoma [MCF7], and human embryonic kidney [Hek-293]) was performed by MTT assay. Among the obtained compounds, compound 7f turned out to be the most potent anticancer agent with significant cytotoxic activity against KB, HepG2, and MCF cancer cell lines.

Twelve new compounds including 2-aminobenzamide derivatives bearing benzothiazole and phenylamine moiety were designed and synthesized. The synthesized compounds were tested their cytotoxic activity against A549 and SW480 tumor cell lines. Compounds 3a and 3c exhibited cytotoxicity toward A549 cell line with IC50 values of 24.59 and 29.59 µM, respectively.

The anti-cancer activity of bannaxanthone E isolated from Garcinia mckeaniana leaves was assessed through a flow cytometric method on human lung SK-LU-1 cancer cells, including cell cycle changes and induction of cell apoptosis. Treatment with bannaxanthone E led to the suppression of cell cycle progression at the G2/M phase to 19.6% at 4 µM, and induced apoptosis via cell morphological changes, increased the fluorescence signal in caspase-3/7 activation, and accumulation of apoptotic cells in the SK-LU-1 line at 4 µM to 25.7%.

Novel 1,4-pyranonaphthoquinone derivatives were successfully synthesized via the microwave-assisted three-component reaction of 1,4-naphthoquinone, malononitrile, and various arylaldehydes in ethanol in the presence of 4-(dimethylamino)pyridine (DMAP) as a catalyst, and subsequently evaluated in terms of their antimicrobial and antifungal activities. This synthetic procedure has the notable advantages of environmental friendliness, short reaction time, good yield, and convenient operation.

For the first time the 4-dimethylaminopyridine (DMAP) catalyzed straightforward and efficient procedure has been developed for the synthesis of 3,3′-(arylmethylene) bis(2-hydroxynaphthalene-1,4-dione) derivatives starting from lawsone (2-hydroxy-1,4-naphthoquinone) and a variety of (hetero)aromatic aldehydes in ethanol under microwave irradiation. Three of nine synthesized compounds are new. This method provides notable advantages over existing procedures including use of non-traditional basic catalyst and environmentally benign solvent, mild reaction conditions, excellent yields, short reaction time and simple workup.

A series of new hydroxamate derivatives of lupane triterpenoids has been designed and successfully synthesized. The synthesized compounds were evaluated for their in vitro antitumor activity using the 3-[4,5-dimethylthiazol-2-yl]−2,5-diphenyltetrazolium bromide-based assay against the human cancer cell lines KB and HepG2. Most of these derivatives possess at least moderate cytotoxic activity and the hydroxamate derivative compounds 3c, 3e, 7a, and 15b could be lead compounds for further optimization to develop novel anticancer agents.

In order to find out the influence of carboxylic acid functionalities in the N-lactam side chains of indenoisoquinolines on cytotoxic activities, several new compounds have been synthesized and structurally characterized by analytical and spectral methods. The incorporation of a carboxylic acid group into the lactam side chain of indenoisoquinolines results in differences in cytotoxicity. The results indicated that compound 18c displayed substantial cytotoxic specificity toward KB and HepG2 cancer cells.

Hemiasterlin is a potent antimitotic agent acting through inhibition of microtubule depolymerization. For this reason, the synthesis of new hemiasterlin derivatives has attracted a lot of interest in the organic chemistry community recently. In this paper, the synthesis and evaluation of the cytotoxicity of new simplified and racemic hemiasterlin derivatives were reported. All of the synthesized analogues were evaluated in vitro for cytotoxic activity against four human cell lines (KB, Hep-G2, LU and MCF7). Most of these analogues possess a strong cytotoxic activity on two human cancer cell lines (KB and Hep-G2) and very weak activity on LU and MCF7 cell lines.

A series of 4-anilinoquinazoline–triazole–AZT hybrids were designed and synthesized as anticancer agents. Their cytotoxic potential has been evaluated by means of a micro-dilution assay against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). The biological results revealed that compounds 4b and 6d showed good anticancer activities against KB, HepG2, and Lu cell lines (IC50 values ranging from 9 μM to 100 μM). Especially, compounds 4b and 6d exhibited up to 3-fold more potent than reference drugs erlotinib hydrochloride and AZT in term of anti-lung cancer activity.

Series of novel artemisinin derivatives were designed and synthesized in which the amino propanol group was bonded to the artemisinin nucleus through C-C linkage. Ten new compounds were thus successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity in KB and HepG2 cancer cell lines.

Series of novel triterpenoid hybrids were designed and synthesized by introducing 2-aminobenzamide moiety at C28 position of triterpenoid derivatives. Thirteen new conjugates were thus successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity in KB and HepG2 cancer cell lines.

Betulin was converted to the corresponding alkyne-functionalized esters and amides and subsequently deployed as substrates for a ‘click’ chemistry-mediated coupling with 3'-azido-3'-deoxythydimine (AZT) to furnish a novel betulin–triazole–AZT hybrid compounds. Eleven new hybrids were thus successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity in KB and HepG2 cancer cell lines.