New sulfonamide-based glycosides incorporated 1,2,3-triazole as cytotoxic agents through VEGFR-2 and carbonic anhydrase inhibitory activity.

New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides' cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC50 = 8.39-16.90 µM against HepG-2 and 19.57-21.15 µM against MCF-7) comparing with doxorubicin (IC50 = 13.76 ± 0.45, 17.44 ± 0.46 µM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC50 = 1.33, 0.38 µM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC50 = 0.43 µM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.

Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro α-glucosidase, α-amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation.

A new series of quinoxaline-sulfonamide derivatives 3-12 were synthesized using fragment-based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline-sulfonamide derivatives were evaluated for antidiabetic and anti-Alzheimer's potential against α-glucosidase, α-amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against α-amylase and α-glucosidase with inhibitory percentages between 24.34 ± 0.01%-63.09 ± 0.02% and 28.95 ± 0.04%-75.36 ± 0.01%, respectively. Surprisingly, bis-sulfonamide quinoxaline derivative 4 revealed the most potent activity with inhibitory percentages of 75.36 ± 0.01% and 63.09 ± 0.02% against α-glucosidase and α-amylase compared to acarbose (IP = 57.79 ± 0.01% and 67.33 ± 0.01%), respectively. Moreover, the quinoxaline derivative 3 exhibited potency as α-glucosidase and α-amylase inhibitory with a minute decline from compound 4 and acarbose with inhibitory percentages of 44.93 ± 0.01% and 38.95 ± 0.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide-quinoxaline derivative 3 emerged as the most active member with inhibitory percentage of 41.92 ± 0.02% compared with donepezil (IP = 67.27 ± 0.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.

Evaluation of antibacterial, cytotoxicity, and apoptosis activity of novel chromene-sulfonamide hybrids synthesized under solvent-free conditions and 3D-QSAR modeling studies.

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.

Synthesis and Assay of Vibrio Quorum Sensing Inhibitors.

Bacteria detect local population numbers using quorum sensing, a method of cell-cell communication broadly utilized to control bacterial behaviors. In Vibrio species, the master quorum sensing regulators LuxR/HapR control hundreds of quorum sensing genes, many of which influence virulence, metabolism, motility, and more. Thiophenesulfonamides are potent inhibitors of LuxR/HapR that bind the ligand pocket in these transcription factors and block downstream quorum sensing gene expression. This class of compounds served as the basis for the development of a set of simple, robust, and educational procedures for college students to assimilate their chemistry and biology skills using a CURE model: course-based undergraduate research experience. Optimized protocols are described that comprise three learning stages in an iterative and multi-disciplinary platform to engage students in a year-long CURE: (1) design and synthesize new small molecule inhibitors based on the thiophenesulfonamide core, (2) use structural modeling to predict binding affinity to the target, and (3) assay the compounds for efficacy in microbiological assays against specific Vibrio LuxR/HapR proteins. The described reporter assay performed in E. coli successfully predicts the efficacy of the compounds against target proteins in the native Vibrio species.

Protocatechuic acid enhanced the selective degradation of sulfonamide antibiotics in Fe(III)/peracetic acid process under actually neutral pH conditions.

The practical application of the Fe-catalyzed peracetic acid (PAA) processes is seriously restricted due to the need for narrow pH working range and poor anti-interference capacity. This study demonstrates that protocatechuic acid (PCA), a natural and eco-environmental phenolic acid, significantly enhanced the removal of sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions (6.0-8.0) by complexing Fe(III). With sulfamethoxazole (SMX) as the model contaminant, the pseudo-first-order rate constant of SMX elimination in PCA/Fe(III)/PAA process was 63.5 times higher than that in Fe(III)/PAA process at pH 7.0, surpassing most of the previously reported strategies-enhanced Fe-catalyzed PAA processes (i.e., picolinic acid and hydroxylamine etc.). Excluding the primary contribution of reactive species commonly found in Fe-catalyzed PAA processes (e.g., •OH, R-O•, Fe(IV)/Fe(V) and 1O2) to SMX removal, the Fe(III)-peroxy complex intermediate (CH3C(O)OO-Fe(III)-PCA) was proposed as the primary reactive species in PCA/Fe(III)/PAA process. DFT theoretical calculations indicate that CH3C(O)OO-Fe(III)-PCA exhibited stronger oxidation potential than CH3C(O)OO-Fe(III), thereby enhancing SMX removal. Four potential removal pathways of SMX were proposed and the toxicity of reaction solution decreased with the removal of SMX. Furthermore, PCA/Fe(III)/PAA process exhibited strong anti-interference capacity to common natural anions (HCO3-, Cl-and NO3-) and humic acid. More importantly, the PCA/Fe(III)/PAA process demonstrated high efficiency for SMX elimination in actual samples, even at a trace Fe(III) dosage (i.e., 5 µM). Overall, this study provided a highly-efficient and eco-environmental strategy to remove sulfonamide antibiotics in Fe(III)/PAA process under actually neutral pH conditions and to strengthen its anti-interference capacity, underscoring its potential application in water treatment.

A python based algorithmic approach to optimize sulfonamide drugs via mathematical modeling.

This article explores the structural properties of eleven distinct chemical graphs that represent sulfonamide drugs using topological indices by developing python algorithm. To find significant relationships between the topological characteristics of these networks and the characteristics of the associated sulfonamide drugs. We use quantitative structure-property relationship (QSPR) approaches. In order to model and forecast these correlations and provide insights into the structure-activity relationships that are essential for drug design and optimization, linear regression is a vital tool. A thorough framework for comprehending the molecular characteristics and behavior of sulfonamide drugs is provided by the combination of topological indices, graph theory and statistical models which advances the field of pharmaceutical research and development.

Design, Synthesis, DFT, docking Studies, and antimicrobial evaluation of novel benzimidazole containing sulphonamide derivatives.

In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC50 363.51 ± 2.54 µM and E. coli IC50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC50 3.51 ± 0.82 µM and E. coli IC50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.

The activity of pyrazolo[4,3-e][1,2,4]triazine and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures.

In the last decade, an increasing interest in compounds containing pyrazolo[4,3-e][1,2,4]triazine moiety is observed. Therefore, the aim of the research was to synthesise a novel sulphonyl pyrazolo[4,3-e][1,2,4]triazines (2a, 2b) and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives (3a, 3b) to assess their anticancer activity. The MTT assay showed that 2a, 2b, 3a, 3b have stronger cytotoxic activity than cisplatin in both breast cancer cells (MCF-7 and MDA-MB-231) and exhibited weaker effect on normal breast cells (MCF-10A). The obtained results showed that the most active compound 3b increased apoptosis via caspase 9, caspase 8, and caspase 3/7. It is worth to note that compound 3b suppressed NF-κB expression and promoted p53, Bax, and ROS which play important role in activation of apoptosis. Moreover, our results confirmed that compound 3b triggers autophagy through increased formation of autophagosomes, expression of beclin-1 and mTOR inhibition. Thus, our study defines a possible mechanism underlying 3b-induced anti-cancer activity against breast cancer cell lines.

QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.

Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties.

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 µg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 µg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.

Molecular docking, synthesis, characteristics and preliminary cytotoxic study of new coumarin-sulfonamide derivatives as histone deacetylase inhibitors.

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Coumarin as cap groups. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound assessed for their cytotoxic activity against hepatoblastoma HepG2 (IC50, I=0.094, II=0.040, III=0.032, IV=0.046, SAHA=0.141) and human colon adenocarcinoma MCF-7 (IC50, I=0.135, II=0.050, III= 0.065, IV=0.059, SAHA=0.107). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6]. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed a comparable cytotoxic result with FDA approved drug (SAHA) toward HepG2 and MCF-7 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.

Sulfonamide modified chitosan oligosaccharide with high nematicidal activity against Meloidogyne incognita.

Chitosan oligosaccharide (COS) modification is a feasible way to develop novel green nematicides. This study involved the synthesis of various COS sulfonamide derivatives via hydroxylated protection and deprotection, which were then characterized using NMR, FTIR, MS, elemental analysis, XRD, and TG/DTG. In vitro experiments found that COS-alkyl sulfonamide derivatives (S6 and S11-S13) exhibited high mortality (>98 % at 1 mg/mL) against Meloidogyne incognita second-instar larvaes (J2s) among the derivatives. S6 can cause vacuole-like structures in the middle and tail regions of the nematode body and effectively inhibit egg hatching. In vivo tests have found that S6 has well control effects and low plant toxicity. Additionally, the structure-activity studies revealed that S6 with a high degree of substitution, a low molecular weight, and a sulfonyl bond on the amino group of the COS backbone exhibited increased nematicidal activity. The sulfonamide group is a potential active group for developing COS-based nematicides.

Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility.

Cardiac myosin activation has been shown to be a viable approach for the treatment of heart failure with reduced ejection fraction. Here, we report the discovery of nelutroctiv (CK-136), a selective cardiac troponin activator intended for patients with cardiovascular conditions where cardiac contractility is reduced. Discovery of nelutroctiv began with a high-throughput screen that identified compound 1R, a muscle selective cardiac sarcomere activator devoid of phosphodiesterase-3 activity. Optimization of druglike properties for 1R led to the replacement of the sulfonamide and aniline substituents which resulted in improved pharmacokinetic (PK) profiles and a reduced potential for human drug-drug interactions. In vivo echocardiography assessment of the optimized leads showed concentration dependent increases in fractional shortening and an improved pharmacodynamic window compared to myosin activator CK-138. Overall, nelutroctiv was found to possess the desired selectivity, a favorable pharmacodynamic window relative to myosin activators, and a preclinical PK profile to support clinical development.

Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl-2.

The approval of venetoclax, a B-cell lymphoma-2 (Bcl-2) selective inhibitor, for the treatment of chronic lymphocytic leukemia demonstrated that the antiapoptotic protein Bcl-2 is a druggable target for B-cell malignancies. However, venetoclax's limited potency cannot produce a strong, durable clinical benefit in other Bcl-2-mediated malignancies (e.g., diffuse large B-cell lymphomas) and multiple recurrent Bcl-2 mutations (e.g., G101V) have been reported to mediate resistance to venetoclax after long-term treatment. Herein, we described novel Bcl-2 inhibitors with increased potency for both wild-type (WT) and mutant Bcl-2. Comprehensive structure optimization led to the clinical candidate BGB-11417 (compound 12e, sonrotoclax), which exhibits strong in vitro and in vivo inhibitory activity against both WT Bcl-2 and the G101V mutant, as well as excellent selectivity over Bcl-xL without obvious cytochrome P450 inhibition. Currently, BGB-11417 is undergoing phase II/III clinical assessments as monotherapy and combination treatment.

Accelerative Solid-State Oxidation Behaviour of Amorphous and Partially Crystalline Venetoclax.

There is a growing focus on solid-state degradation, especially for its relevance in understanding interactions with excipients. Performing a solid-state degradation of Venetoclax (VEN), we delve into VEN's stability in different solid-state oxidative stress conditions, utilizing Peroxydone™ complex and urea peroxide (UHP). The investigation extends beyond traditional forced degradation scenarios, providing insights into VEN's behavior over 32 h, considering temperature and crystallinity conditions. Distinct behaviors emerge in the cases of Peroxydone™ complex and UHP. The partially crystalline (PC-VEN) form proves more stable with Peroxydone™, while the amorphous form (A-VEN) shows enhanced stability with UHP. N-oxide VEN, a significant degradation product, varies between these cases, reflecting the impact of different oxidative stress conditions. Peroxydone™ complex demonstrates higher reproducibility and stability, making it a promising option for screening impurities in solid-state oxidative stress scenarios. This research not only contributes to the understanding of VEN's stability in solid-state but also aids formulators in anticipating excipient incompatibilities owing to presence of reactive impurities (peroxides) and oxidation in the final dosage form.

Exploration and structure-activity relationship research of benzenesulfonamide derivatives as potent TRPV4 inhibitors for treating acute lung injury.

RN-9893, a TRPV4 antagonist identified by Renovis Inc., showcased notable inhibition of TRPV4 channels. This research involved synthesizing and evaluating three series of RN-9893 analogues for their TRPV4 inhibitory efficacy. Notably, compounds 1b and 1f displayed a 2.9 to 4.5-fold increase in inhibitory potency against TRPV4 (IC50 = 0.71 ± 0.21 µM and 0.46 ± 0.08 µM, respectively) in vitro, in comparison to RN-9893 (IC50 = 2.07 ± 0.90 µM). Both compounds also significantly outperformed RN-9893 in TRPV4 current inhibition rates (87.6 % and 83.2 % at 10 µM, against RN-9893's 49.4 %). For the first time, these RN-9893 analogues were profiled in an in vivo mouse model, where intraperitoneal injections of 1b or 1f at 10 mg/kg notably mitigated symptoms of acute lung injury induced by lipopolysaccharide (LPS). These outcomes indicate that compounds 1b and 1f are promising candidates for acute lung injury treatment.

Synthesis, molecular modelling, and antibacterial evaluation of new sulfonamide-dyes based pyrrole compounds.

In this study, we synthesized new series of 5-oxo-2-phenyl-4-(arylsulfamoyl)sulphenyl) hydrazono)-4,5-dihydro-1H-pyrrole-3-carboxylate hybrids 4a-f with the goal of overcoming sulfonamide resistance and identifying novel therapeutic candidates by chemical changes. The chemical structures of the synthesized hybrids were established over the spectroscopic tools. The frontier molecular orbitals configuration and energetic possessions of the synthesized compounds were discovered utilizing DFT/B3LYP/6-311++ G** procedure. The 3D plots of both HOMO and LUMO showed comparable configuration of both HOMO and LUMO led to close values of their energies. Amongst the prepared analogues, the sulfonamide hybrids 4a-f, hybrid 4a presented potent inhibitory towards S. typhimurium with (IZD = 15 mm, MIC = 19.24 µg/mL) and significant inhibition with (IZD = 19 mm, MIC = 11.31 µg/mL) against E.coli in contrast to sulfonamide (Sulfamethoxazole) reference Whereas, hybrid 4d demonstrated potent inhibition with (IZD = 16 mm, MIC = 19.24 µg/mL) against S. typhimurium with enhanced inhibition against E. Coli, Additionally, the generated sulfonamide analogues'' molecular docking was estimated over (PDB: 3TZF and 6CLV) proteins. Analogue 4e had the highest documented binding score as soon as linked to the other analogues. The docking consequences were fitting and addressed with the antibacterial valuation.

Synthesis and Properties of Oligonucleotides Containing LNA-Sulfamate and Sulfamide Backbone Linkages.

Oligonucleotides hold great promise as therapeutic agents but poor bioavailability limits their utility. Hence, new analogues with improved cell uptake are urgently needed. Here, we report the synthesis and physical study of reduced-charge oligonucleotides containing artificial LNA-sulfamate and sulfamide linkages combined with 2'-O-methyl sugars and phosphorothioate backbones. These oligonucleotides have high affinity for RNA and excellent nuclease resistance.

Sulfonamides as anticancer agents: A brief review on sulfonamide derivatives as inhibitors of various proteins overexpressed in cancer.

Sulfonamides have gained prominence as versatile agents in cancer therapy, effectively targeting a spectrum of cancer-associated enzymes. This review provides an extensive exploration of their multifaceted roles in cancer biology. Sulfonamides exhibit adaptability by acting as tyrosine kinase inhibitors, disrupting pivotal signaling pathways in cancer progression. Moreover, they disrupt pH regulation mechanisms in cancer cells as carbonic anhydrase inhibitors, inhibiting growth, and survival. Sulfonamides also serve as aromatase inhibitors, interfering with estrogen synthesis in hormone-driven cancers. Inhibition of matrix metalloproteinases presents an opportunity to impede cancer cell invasion and metastasis. Additionally, their emerging role as histone deacetylase inhibitors offers promising prospects in epigenetic-based cancer therapies. These diverse roles underscore sulfonamides as invaluable tools for innovative anti-cancer treatments, warranting further exploration for enhanced clinical applications and patient outcomes.

Implications of polystyrene and polyamide microplastics in the adsorption of sulfonamide antibiotics and their metabolites in water matrices.

Microplastics (MP) and antibiotics coexist in the environment and their combined exposure represents a source of increasing concern. MP may act as carriers of antibiotics because of their sorption capacity. Knowledge of the interactions between them may help improve understanding of their migration and transformation. In this work, the adsorption behaviour of a group of sulfonamides and their acetylated metabolites on different sizes of polyamide (PA) and polystyrene (PS) MP were investigated and compared. Sulfonamides were adsorbed on both MP (qmax up to 0.699 and 0.184 mg/g, for PA and PS, respectively) fitting to a linear isotherm model (R2 > 0.835). A low particle size and an acidic and salinity medium significantly enhances the adsorption capacity of sulfonamides (i.e. removal of sulfamethoxazole increased from 8 % onto 3 mm PA pellets to 80 % onto 50 mm of PA pellets). According to characterization results, adsorption mechanism is explained by pore filling and hydrogen bonds (for PA) and hydrophobic interactions (for PS). After adsorption, surface area was increased in both MP as result of a potential ageing of the particles and the intensity of XRD peaks was higher denoting a MP structure more amorphized. Metabolites were adsorbed more efficiently than their parent compounds on PS while the opposite effect was observed on PA explained by the acetylation of the amine group and, subsequently the reduction of hydrogen bond interactions. Although the dissolved organic matter inhibits sulfonamides adsorption, removal up to 65.2 % in effluent wastewater and up to 72.1 % in surface water were observed in experiments using real matrices denoting the role of MP as vectors of sulfonamide antibiotics in aquatic media.