In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc, copper, silver, and tin and characterized by spectroscopic techniques and biological assays. Docking analyses revealed six complexes with favorable binding interactions, which were further subjected to in vitro anticancer activity. The complexes 6b and 6c displayed the most potent antiproliferative activity against MCF-7 cell lines with an IC50 value of 11.9 ± 0.27 and 12.0 ± 0.14 μM, respectively, as compared with the standard doxorubicin with an IC50 value of 0.90 ± 0.14 μM. In vivo anticonvulsant activities of the compounds were evaluated by the subcutaneous pentylenetetrazole model and neurotoxic activities by the minimal motor impairment model. The neurotoxicity of targeted compounds was measured using the rotating rod (ROT) method. Computational studies were carried out using the reported crystal structures of multidrug-resistant protein (PDB-ID: 2KAV) and dihydrofolate reductase (PDB-ID: 3GHW), indicating that the compound 6c showed significant interactions at the voltage-gated sodium ion channel in the brain and at dihydrofolate reductase enzyme in the breast. Certain metal complexes of Schiff base ligands (e.g., 6c) were found to possess the most potent anticancer, anticonvulsant, and neurotoxic potential than lamotrigine alone.

Purpose: To study the enzyme inhibition activity of various sulfonamides derived from dagenan chloride. (2) Methods: The synthesis of N-(naphthalen-1-yl)-4-acetamidobenzenesulfonamide (3) was carried out by gearing up 1-naphthylamine (1) with dagenan chloride

Apigenin is a phytochemical obtained from Chamomilla recutita. Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10−9–10−4) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-α and TGF 1-β) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M3 receptors, KATP channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M2 receptors, KIR channels, and β-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-β/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.

Interstitial cystitis (IC) is the principal unwanted effect associated with the use of cyclophosphamide (CYP). It results in increased oxidative stress, overexpression of proinflammatory cytokines, and bladder overactivity. Patients receiving CYP treatment had severely depreciated quality of life, as the treatment available is not safe and effective. The goal of this study was to assess the protective effect of caftaric acid in CYP-induced IC. IC was induced in female Sprague Dawley by injecting CYP (150 mg/kg, i.p.). In the present study, oral administration of caftaric acid (20, 40, and 60 mg/kg) significantly decreased inflammation. Caftaric acid significantly increased SOD (93%), CAT (92%), and GSH (90%) while decreased iNOS (97%), IL-6 (90%), TGF 1-β (83%), and TNF-α (96%) compared to the diseased. DPPH assay showed the antioxidant capacity comparable to ascorbic acid. Molecular docking of caftaric acid with selected protein targets further confirmed its antioxidant and anti-inflammatory activities. The cyclophosphamide-induced bladder overactivity had been decreased possibly through the inhibition of M3 receptors, ATP-sensitive potassium channels, calcium channels, and COX enzyme by caftaric acid. Therefore, our findings demonstrate that caftaric acid has a considerable protective role against CYP-induced IC by decreasing the oxidative stress, inflammation, and bladder smooth muscle hyperexcitability. Thus, caftaric acid signifies a likely adjuvant agent in CYP-based chemotherapy treatments.