Design, synthesis, molecular modeling, and biological evaluation of sulfanilamide-imines derivatives as potential anticancer agents

Abstract

A series of sulfanilamide Schiff base derivatives (1 to 15) have been designed as potential antitubulin agents depending on the chemical structures of combretastatine A-4 and isoquinoline sulfamate (antimitotic agents under investigation). The designed compounds were synthesized by microwave chemical synthesis, their purity was confirmed by melting point and HPLC and chemical structures were determined by FT-IR, UV, and 1H and 13C-NMR spectroscopic techniques. The synthesized compounds have been docked in the colchicine binding site of β-tubulin using molecular modeling programs and the antitumor activities were screened on human breast and lung cancer cells by cell counting assay. Some tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC50 range of 90 to 166 μM. With regarding broad-spectrum activity, compounds 4, 8, and 13 have shown potent antitumor activity against human breast and human lung cells with IC50 range of 96 to 140 μM. The obtained results suggest that the sulfanilamide Schiff base derivatives might potentially constitute an interesting novel class of anticancer agents, which deserve further studies.

4-{[4-(Dimethylamino)benzylidene]amino}benzenesulfonamide

“…For the biological and physical properties of sulfonamides and their derivatives and for their pharmacological applications, see: Chohan & Shad (2012); Domagk (1935); Khalil et al (2009); Sharaby (2007); Lin et al (2008); Maren (1967); Mohamed et al (2013); Saluja et al (2014); Supuran et al (1996); Tü rkmen et al (2005). For related structures, see: Idemudia et al (2012); Loughrey et al (2009).…”

“…Sulfonamide derivatives are very important because of their varied structures and biological activities (Domagk, 1935). This type of derivative displays interesting enzymatic inhibition towards the carbonic anhydrase (CA) isozymes CA I, II, IV, IX and XII (Supuran et al, 1996;Türkmen et al, 2005;Saluja et al, 2014) and the cyclo-oxygenase (COX) enzymes COX-1 and COX-2 (Lin et al, 2008) are still widely used as antimicrobial drugs, antithyroid agents, antibacterial, antifungal, antitumor, antibiotics, acid-base indicator, potential anticancer agents (Maren, 1967;Khalil et al, 2009;Sharaby, 2007;Mohamed et al, 2013;Chohan & Shad, 2012). The title compound was synthesized and its crystal structure is reported on herein.…”

“…The title compound was synthesized according to the literature method with some modifications (Khalil et al, 2009;Sharaby, 2007;Lin et al, 2008;Supuran et al, 1996;Mohamed et al, 2013). Sulfonamide (0.172 g, 1.0 mmol) in absolute ethanol (20 ml) was added to 4-(dimethylamino)benzaldehyde (0.149 g, 1.0 mmol) in absolute ethanol (20 ml), and 2 drops of formic acid were added as catalyst.…”

Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs

“…Thus, we use CA-4 as a lead molecule for synthesis of new derivatives and more studied as tubulin inhibitors [5]. It is formed of three parts (2 carbons bridge, ring A and ring B) [6] (Figure 1(b)).…”

Theoretical and experimental investigation of 4-[(2-hydroxy-3-methylbenzylidene)amino]benzenesulfonamide: Structural and spectroscopic properties, NBO, NLO and NPA analysis

“…The derivatives of sulfonamide are very important because of their varied structures and biological activities [1]. These types of derivatives display interesting enzymatic inhibition towards the carbonic anhydrase (CA) isozymes CA I, II, IV, IX, and XII [2][3][4][5] and the cyclo-oxogenase (COX) enzymes COX-1 and COX-2 [6] still widely used for conditions such as antimicrobial drugs, antithyroid agents, antibacterial, antifungal, antitumor, antibiotics, acid-base indicator, potential anticancer agents [7][8][9][10][11].…”