N-Cycloamino substituent effects on the packing architecture of ortho-sulfanilamide molecular crystals and their in silico carbonic anhydrase II and IX inhibitory activities

Abstract

In the search for new `sulfa drugs' with therapeutic properties, o-nitrosulfonamides and N-cycloamino-o-sulfanilamides were synthesized and characterized using techniques including 1H NMR, 13C NMR and FT–IR spectroscopy, and single-crystal X-ray diffraction (SC-XRD). The calculated density functional theory (DFT)-optimized geometry of the molecules showed similar conformations to those obtained by SC-XRD. Molecular docking of N-piperidinyl-o-sulfanilamide and N-indolinyl-o-sulfanilamide supports the notion that o-sulfanilamides are able to bind to human carbonic anhydrase II and IX inhibitors (hCA II and IX; PDB entries 4iwz and 5fl4). Hirshfeld surface analyses and DFT studies of three o-nitrosulfonamides {1-[(2-nitrophenyl)sulfonyl]pyrrolidine, C10H12N2O4S, 1, 1-[(2-nitrophenyl)sulfonyl]piperidine, C11H14N2O4S, 2, and 1-[(2-nitrophenyl)sulfonyl]-2,3-dihydro-1H-indole, C14H12N2O4S, 3} and three N-cycloamino-o-sulfanilamides [2-(pyrrolidine-1-sulfonyl)aniline, C10H14N2O2S, 4, 2-(piperidine-1-sulfonyl)aniline, C11H16N2O2S, 5, and 2-(2,3-dihydro-1H-indole-1-sulfonyl)aniline, C14H14N2O2S, 6] suggested that forces such as hydrogen bonding and π–π interactions hold molecules together and further showed that charge transfer could promote bioactivity and the ability to form biological interactions at the piperidinyl and phenyl moieties.

Synthesis and molecular docking studies of novel tricyclic and angular tetracyclic benzothiadiazines via sp3‐C‐Hactivation as potential colon cancer inhibitors

“…Crystals were obtained from the slow solvent evaporation of the requisite eluates at ambient temperature. Compounds 14–16 were published in our previous paper Kolade et al [30], and compound 17 was published in Kolade et al [29].…”

“…FT-IR, MS, 1 H-and 13 C-NMR spectra of the synthesized compounds (18)(19)(20)(21)(22) are presented in the Data S1. 5.2.7 | Synthesis of N-cycloamino-4-substituted-2-sulfanilamides (27)(28)(29)(30)(31) An evacuated, nitrogen gas-filled round-bottomed flask was charged with N-cycloamino-o-nitrobenzenesulfonamides (18-22) (15.63 mmol) dissolved in ethanol (30 mL) at ambient temperature, and 10% palladium-on-charcoal catalyst (3.35 mol%) was added with stirring. Hydrogen gas was then introduced via a balloon, and stirring continued at ambient temperature for 12 h. The reaction mixture was filtered, and the solvent was evaporated in vacuo.…”

“…The synthesis of the tricyclic and angular tetracyclic benzothiadiazines started with the formation of nitro sulfonamides under basic conditions as previously reported by us [14,29] and amino sulfonamide under reduction with palladium/charcoal in good to high yield [30] Scheme 1. The result of the reduction of the nitro adduct is as shown in Table 1, five of the amides are reported for the first time (entry 5 to 9).…”

“…S C H E M E 1 Synthesis of N-cycloamino-4-substituted-2-nitrobenzenesulfonamides (14)(15)(16)(17)(18)(19)(20)(21)(22) and their sulfanilamide analogs (23)(24)(25)(26)(27)(28)(29)(30)(31).…”

Synthesis, crystal structure and in-silico evaluation of arylsulfonamide Schiff bases for potential activity against colon cancer

“…N 1 -(5 1 -Substituted-2 1 -hydroxybenzylidenyl)-N-cycloamino-2-sulfanilamides 17-23 were prepared from the reaction of N-cycloamino-2-sulfanilamides 10-13 [as reported previously by Kolade et al (2022)] with substituted o-salicylaldehyde either at room temperature or under reflux to obtain the required Schiff bases in good yields (57-80%). Only o-salicylaldehyde and N-piperidinyl-2-sulfanilamide gave the required Schiff base at room temperature, and the others were refluxed to obtain the desired products.…”