RESUMO
In this study, eleven novel chromene sulfonamide hybrids were synthesized by a convenient method in accordance with green chemistry. At first, chromene derivatives (1-9a) were prepared through the multi-component reaction between aryl aldehydes, malononitrile, and 3-aminophenol. Then, synthesized chromenes were reacted with appropriate sulfonyl chlorides by grinding method to give the corresponding chromene sulfonamide hybrids (1-11b). Synthesized hybrids were obtained in good to high yield and characterized by IR, 1HNMR, 13CNMR, CHN and melting point techniques. In addition, the broth microdilution assay was used to determine the minimal inhibitory concentration of newly synthesized chromene-sulfonamide hybrids. The MTT test was used to determine the cytotoxicity and apoptotic activity of the newly synthesized compounds against fibroblast L929 cells. The 3DQSAR analysis confirmed the experimental assays, demonstrating that our predictive model is useful for developing new antibacterial inhibitors. Consequently, molecular docking studies were performed to validate the findings of the 3D-QSAR analysis, confirming the potential binding interactions of the synthesized chromene-sulfonamide hybrids with the target enzymes. Molecular docking studies were employed to support the 3D-QSAR predictions, providing insights into the binding interactions between the newly synthesized chromene-sulfonamide hybrids and their target bacterial enzymes, thereby reinforcing the potential efficacy of these compounds as antibacterial agents. Also, some of the experimental outcomes supported or conflicted with the pharmacokinetic prediction (especially about compound carcinogenicity). The performance of ADMET predictor results was assessed. The work presented here proposes a computationally driven strategy for designing and discovering a new sulfonamide scaffold for bacterial inhibition.
Assuntos
Antibacterianos , Apoptose , Benzopiranos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Sulfonamidas , Sulfonamidas/química , Sulfonamidas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Benzopiranos/química , Benzopiranos/farmacologia , Apoptose/efeitos dos fármacos , Camundongos , Animais , Linhagem CelularRESUMO
Sulfonamide compounds, also known as sulfa drugs, are a significant class of synthetic bacteriostatic antimicrobials and were the primary source of therapy against bacterial infections before the introduction of penicillin in 1941. Hybridization of sulfonamides with various pharmaceutically active heterocyclic moieties leads to sulfonamide hybrids with a wide variety of biological activities. Part B of this review presents the most recent advances in designing and developing more two-component sulfonamide hybrids containing triazole, thiadiazole, triazine, oxazole/ benzoxazole, isoxazole, oxadiazole, imidazole, benzimidazole, furan, benzofuran, thiophene, pyrrole, indazole, tetrazole, chromene/ chromone, pyridazine, quinoxaline, acridine, phthalazine, and xanthone between 2015 and 2020. We hope this review helps the scientific community in designing more useful sulfonamide hybrid drugs.
Assuntos
Anti-Infecciosos , Sulfonamidas , Humanos , Sulfanilamida , Benzopiranos , PenicilinasRESUMO
Sulfonamides constitute an important class of drugs, with many types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, anti-obesity, diuretic, hypoglycemic, antithyroid, antitumor, and anti-neuropathic pain activities. The sulfonamides are the compounds that have general formula R-SO2NHR', where the functional group is bound to aromatic, heterocycle, and aliphatic groups. The nature of the R and R' moiety is variable, starting with hydrogen and ranging to a variety of moieties incorporating organic compounds such as coumarin, isoxazole, tetrazole, pyrazole, pyrrole, and so many other pharmaceutical active scaffolds that lead to a considerable range of hybrids named as sulfonamide hybrids. Part A of this review presents the most recent advances in designing and developing two-component sulfonamide hybrids containing coumarin, indole, quinoline, isoquinoline, chalcone, pyrazole/pyrazoline, quinazoline, pyrimidine, thiazole, benzothiazole, and pyridine between 2015 and 2020. Specifically, the authors review the scientific reports on the synthesis and biological activity of this kind of hybrid agent.
Assuntos
Inibidores da Anidrase Carbônica , Anidrases Carbônicas , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Pirazóis , Relação Estrutura-Atividade , Sulfanilamida , Sulfonamidas/farmacologia , TiazóisRESUMO
Sulfonamides, with the general formula R-SO2NR1R2, have attracted great attention since the early discovery of sulfonamide-containing antibacterial drugs. The combinations of certain sulfonamides and other drug molecules to form sulfonamide hybrids are being used to develop novel formulations with greater effectiveness and in a huge range of therapeutic applications such as antimicrobial, antifungal, anti-inflammatory, antitubercular, antiviral, antidiabetic, antiproliferative, carbonic anhydrase inhibitor, antimalarial, anticancer and other medicinal agents. Part C of this review presents recent advances in designing and developing multicomponent sulfonamide hybrids containing more than one biologically active heterocycle, such as coumarin, indole, pyridine, pyrimidine, pyrazole, triazole, oxazole, oxadiazole, triazine, quinazoline, and thiadiazol. This review aims to highlight the status of the hybridization technique in synthesizing biological and computational studies of novel sulfonamide hybrids that were designed and presented between 2016 and 2020.