Synthesis, Characterization and Anti-proliferation Activities of Novel Cyano Oximino Sulfonate Esters

Abstract

A series of novel cyano oximino sulfonate derivatives were prepared from the reaction of arylsulfonyl chloride with different cyanoacetamide-based oximes ranging from the simplest unsubstituted amide to analogues containing N-ethyl (mimicking the Oxyma template), N-piperidinyl and N-morpholinyl chains. In addition, the cyano oximes, N-hydroxybenzimidoyl cyanide and N-hydroxypicolinimidoyl cyanide were also used in the synthesis of the novel cyano oximino sulfonate derivatives. The structures of the prepared compounds were confirmed by 1 H-NMR, 13 C-NMR, and elemental analysis. The preliminary bioassays showed that some of the title compounds, such as 2-oxo-2-(piperidin-1-yl)-N-(tosyloxy)acetimidoyl cyanide (TsPipOx), N-(tosyloxy)benzimidoyl cyanide (TsPhOX), N-(naphthalen-2-ylsulfonyloxy)-2-oxo-2-(piperidin-1-yl)acetimidoyl cyanide (NpsPipOx), 2-amino-N-(naphthalen-2-ylsulfonyloxy)-2-oxoacetimidoyl cyanide (NpsAmOx), N-(naphthalen-2-ylsulfonyloxy)benzimidoyl cyanide (NpsPhCN), and N-(naphthalen-2-ylsulfonyloxy)picolinimidoyl cyanide (NpsPyCN), showed anti-proliferation effect on the mouse fibroblast L929. The calculated IC 50 -values were ranging between 36.5 µg/mL and 0.235 mg/mL. However the anti-proliferation effects seem to be cytostatic rather than cytotoxic. The compounds only minimize the growth activity without completely killing the cells.Key words phenylsulfonate; naphthylsulfonate; oxime; anti-proliferation; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT-assay) Oximes are one of the most versatile building blocks in organic and organometallic chemistry. The substituent pending at α-position account for the specific properties of each oxime, such as dissociation constant, solubility, chelating ability, etc.1-3) Their multifaceted nature derives in a broad range of applications in chemistry in addition to be biologically relevant moieties. 4-7)Biologically active heterocyclic compounds containing amine moiety, specifically piperidine and morpholine skeletons are attractive targets of organic synthesis owing to their pharmacological activity and wide occurrence in nature. 8,9) Piperidines are known to have central nervous system (CNS) depressant activity at low dosage levels but stimulant activity with increased doses. In addition, the piperidine skeleton possesses analgesic, ganglionic blocking and anesthetic properties.10,11) Morpholine derivatives have been reported to possess antiinflammatory [12][13][14] antimicrobial 15,16) and central nervous system activities. 17,18)The sulfonate ester is considered an important class in the sulfonylation reaction for the synthesis of sulfonamide which exhibits a wide range of biological activities. [19][20][21][22] Sulfonylation is also used as a protection technique for OH and NH functionalities, as it enables crystallization and the protecting group can be selectively cleaved in the presence of acid-labile tert-butyl-based groups by using HCl or HBr in alcohol 23) or in aprotic solvents such as ethylacetate or dimethylformamide. 24,...

Crystal structure of 1-methyl-3-[((naphthalen-2-ylsulfonyl)oxy)imino]indolin-2-one, C19H14N2O4S

“…Some oxime derivatives have been also examined as useful pharmacophores in a range of therapeutic agents and considered as bioisosteres which provide a series of potent antiviral agents [9][10][11][12][13]. Recently, O-acyl and O-arylsulfonyl derivatives of isatin 3-oximes have been synthesized and their reactivity towards alcohols and amines has been reported [14][15][16]. O-sulfonyl derivatives were reported with better reactivity than their analogous O-acyl derivatives.…”

Synthesis, crystallographic characterization, DFT and TD-DFT studies of Oxyma-sulfonate esters

“…The two oximes 8 and 9 were synthesized according to the previously reported method 20 and used for the preparation of the sulfonate esters 11, 14 and 16. 20 2.2a General method for the synthesis of sulfonate esters: The reported method 20 was modified as follows:…”

“…The analysis showed that these compounds (10)(11)(12)(13)(14)(15) have growth inhibition activity on L929 cells. 20 Herein, we report a modified method for the synthesis of the sulfonate esters using dichloromethanewater (two-phase method) in the presence of sodium carbonate for the scavenging of the HCl. X-ray crystallography was used to determine the structures of the three prepared sulfonate esters.…”

Copper(II)-Dioxygen Facilitated Activation of Nitromethane: Nitrogen Donors for the Synthesis of Substituted 2-Hydroxyimino-2-phenylacetonitriles and Phthalimides

“…Nitrogen is one of the most important elements that constitute organisms and plays an important role in life activities of biomolecules. Cyano-oxime compounds and their derivatives have shown tremendous potentials for the development of a variety of biological compounds such as herbicides, drugs, and antibacterial agents (Gerasimchuk et al, 2008;El-Faham et al, 2014). The presence of two important functional groups in a single molecule makes them widely applicable for the synthesis of nitrogenous organic compounds in chemical engineering (Robertson et al, 2005;Aakeröy et al, 2012;Soliman et al, 2017).…”