Propan-2-yl 2-(1,1,3-trioxo-2,3-dihydro-1λ<sup>6</sup>,2-benzothiazol-2-yl)acetate

Zia‐ur‐Rehman, Muhammad; Shahid, Bilal; Siddiqui, Hamid Latif; Ahmad, Tanveer; Parvez, Masood

doi:10.1107/s1600536812036148

Cited by 1 publication

(1 citation statement)

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“…Therefore, different alkyl side chains, with either electron-withdrawing or electron-donating groups, can easily be bonded to the nitrogen atom in the isothiazaole ring of the saccharin moiety. Hence, a variety of N -alkyl saccharins with nitrile, ester alkoxy, and heteroaryls have been prepared by this method in refluxing dimethylformamide [ 37 , 38 , 39 , 40 , 41 , 42 ]. In some literature reports, sodium or potassium salts of saccharin can be prepared in situ by heating the saccharin with the alkyl halides in DMF directly [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Anticancer, Antioxidant, Anti-Inflammatory, Antimicrobial Activities, Molecular Docking, and DFT Studies of Sultams Derived from Saccharin

et al. 2022

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A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a–g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (1H-NMR, 13C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (Egap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.

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