Synthesis of novel 4-(1H-benzimidazol-2-yl)benzene-1,3-diols and their cytotoxic activity against human cancer cell lines

Abstract

One-pot synthesis of new biologically active 4-(1H-benzimidazol-2-yl)benzene-l,3-diols has been developed. The compounds were prepared by the reaction of aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s with benzene-l,2-diamines. Their structures were identified using elemental, IR, (1)H-NMR, and mass spectra analyses. The developed method offers short reaction times, relatively large-scale synthesis, easy and quick isolation of the products, and good yields. The cytotoxicity in vitro against the 4 human cancer cell lines: SW707 (rectal), HCV29T (bladder), A549 (lung), and T47D (breast) was determined. The antiproliferative properties of some compounds studies were stronger than those of cisplatin, which was used as a comparator drug.

Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues

“…The log k w and S parameters obtained by the extrapolation technique are commonly used as lipophilicity descriptors [32,49,50]. To obtain better results, the previously described compound 4-(1H-benzimidazol-2-yl)-benzene -1,3-diol (bib-1,3-diol) as a parent compound was included in the biological screening (Tables 1 and 5) [26]. The structure-activity elucidation shows that the presence of the third -OH group in the benzenediol moiety (compounds 7 and 10) or -NO 2 (13, 14), particularly -CN (11, 12) on the benzimidazole ring decreases significantly the inhibitory potency of the compounds against both enzymes.…”

“…Previously studied 4-(1H-benzimidazol-2-yl)benzene-1,3-diols and their metal complexes showed significant anticancer and antimicrobial potencies [25][26][27][28]. Polyphenol derivatives are commonly known as antioxidants.…”

1-(Pyridin-4-yl)-3-(2,4,6-trichlorophenyl)benz[4,5]imidazo[1,2-d][1,2,4]triazin-4(3H)-one

“…Compounds containing a benzimidazole core have been investigated as pharmaceuticals (Karpiń ka et al, 2011;Singh et al, 2010) and therapeutic agents (Biron, 2006;Pescovitz, 2008), and feature as commercial drugs such as omeprazole (Prilosec), pantoprazole (Protonix), vermox and mibefradil (Karpin'ska et al, 2011). Several benzimidazole based compounds show anti-cancer activity (Thomas et al, 2007), some exhibiting cytotoxic effects against a panel of human cancer cell lines (Refaat, 2010).…”

Synthesis, Spectral and Theoretical Characterization of 5,6-Dichloro/Dimethyl-2-(2´,3´/2´,4´/2´,5´/3´,4´/3´,5´-Dimethoxyphenyl)-1H-Benzimidazoles

“…The other important benzimidazol derivatives that are used as drugs are: thiabendazole [4,5], albendazole, mebendazole, fl ubendazole [6,7] astemizole [8] and fenbendazole [9]. The high therapeutic properties of the related drugs have encouraged the medicinal chemists to synthesize a large number of novel chemotherapeutic agents [10][11][12]. They displayed many biological activities, such as: antiviral [13] and antitumoral [14]; antifungal and antimycotic [15]; antihistaminic and antiallergic [16]; antimicrobial [17][18][19][20] and antihelminthic activity [21]; all are unique characteristics known for benzimidazole derivatives [10].…”