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Molecules (Basel, Switzerland) May 2021The synthesis of novel triphenyltin(IV) compounds, PhSnL ( = 1-3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), , and the new propanoic acid derivatives...
The synthesis of novel triphenyltin(IV) compounds, PhSnL ( = 1-3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), , and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, , and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, , has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC values ranging from 0.100 to 0.758 µM. According to the CV assay (IC = 0.218 ± 0.025 µM), complex demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that induces caspase-independent apoptosis in MCF-7 cells.
Topics: Animals; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Gentian Violet; HT29 Cells; HeLa Cells; Humans; In Vitro Techniques; Inhibitory Concentration 50; Ligands; MCF-7 Cells; Mass Spectrometry; Metals; Mice; NIH 3T3 Cells; Neoplasms; Organotin Compounds; Reactive Nitrogen Species; Reactive Oxygen Species
PubMed: 34071809
DOI: 10.3390/molecules26113199 -
Biomedicines Jun 2021SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase...
Proof-of-Concept for the Analgesic Effect and Thermoregulatory Safety of Orally Administered Multi-Target Compound SZV 1287 in Mice: A Novel Drug Candidate for Neuropathic Pain.
SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase copper containing 3, transient receptor potential ankyrin 1 and vanilloid 1 (TRPV1) receptors. Mainly under acidic conditions, it is transformed to the cyclooxygenase inhibitor oxaprozin, which is ineffective for neuropathy. Therefore, an enterosolvent capsule is suggested for oral formulation, which we investigated for nociception, basic kinetics, and thermoregulatory safety in mice. The antihyperalgesic effect of SZV 1287 (10, 20, 50, and 200 mg/kg, p.o.) was determined in partial sciatic nerve ligation-induced traumatic neuropathy by aesthesiometry, brain and plasma concentrations by HPLC, and deep body temperature by thermometry. Its effect on proton-induced TRPV1 activation involved in thermoregulation was assessed by microfluorimetry in cultured trigeminal neurons. The three higher SZV 1287 doses significantly, but not dose-dependently, reduced neuropathic hyperalgesia by 50% of its maximal effect. It was quickly absorbed; plasma concentration was stable for 2 h, and it entered into the brain. Although SZV 1287 significantly decreased the proton-induced TRPV1-mediated calcium-influx potentially leading to hyperthermia, it did not alter deep body temperature. Oral SZV 1287 inhibited neuropathic hyperalgesia and, despite TRPV1 antagonistic action and brain penetration, it did not influence thermoregulation, which makes it a promising analgesic candidate.
PubMed: 34209525
DOI: 10.3390/biomedicines9070749 -
Tetrahedron Letters Feb 20162-(Halomethyl)-4,5-diphenyloxazoles are effective, reactive scaffolds which can be utilized for synthetic elaboration at the 2-position. Through substitution reactions,...
2-(Halomethyl)-4,5-diphenyloxazoles are effective, reactive scaffolds which can be utilized for synthetic elaboration at the 2-position. Through substitution reactions, the chloromethyl analogue is used to prepare a number of 2-alkylamino-, 2-alkylthio- and 2-alkoxy-(methyl) oxazoles. The 2-bromomethyl analogue offers a more reactive alternative to the chloromethyl compounds and is useful in the C-alkylation of a stabilized (malonate) carbanion as exemplified by a concise synthesis of Oxaprozin.
PubMed: 26989270
DOI: 10.1016/j.tetlet.2016.01.016 -
Nephron 1996
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Back Pain; Capillaries; Complement C3; Edema; Epithelium; Glomerulonephritis, Membranous; Humans; Hypertension; Immunoglobulin G; Kidney Glomerulus; Leg; Male; Nifedipine; Oxaprozin; Propionates
PubMed: 8893177
DOI: 10.1159/000189356