Novel Pyrazolines and Benzothiazepines as Tubulin Polymerization Inhibitors: Synthesis, Biological Evaluation, and Molecular Docking

Abstract

Synthesis, biological evaluation, and molecular docking of pyrazoline-linked benzenesulfonamides and diaryl 1,5-benzothiazepines prepared from new chalcones are described and elucidated. Novel compounds were studied for their in vitro anticancer profiles on HepG2, HEK-293, MCF-7, and MDA-MB-231 cancer cell lines, where, compounds IIb, III, and IVe demonstrated high to moderate cell proliferation inhibition activity. Compound IIb was further assessed for tubulin polymerization inhibition effects due to its high potency, which showed superior suppression compared to the reference drug. It induced cell cycle cessation at the G2/M phase and accumulation of cells in the pre-G1 phase, preventing its mitotic cycle. In addition, compound IIb activated caspase-7, mediating apoptosis of HepG2 cells. These findings, along with molecular docking and pharmacophore constructed models, provide a new scaffold of cytotoxic agents targeting tubulin.

From screening to the hectogram scale: sustainable electrochemical synthesis of mefenpyr-diethyl

“…18 Conventionally, pyrazolines and pyrazoles are synthesized by condensation of hydrazones with 1,3-diketones, 19,20 2-ynones, 21 or 2-enones. 22 Yet, these strategies suffer from an often-unsatisfying regioselectivity and difficult-to-obtain starting materials. Other strategies rely on oxidative synthesis of hydrazonoyl halides; subsequent pyrazoline or pyrazole formation is achieved via base-promoted liberation of the corresponding nitrile imine and [3 + 2] cycloaddition with a dipolarophile.…”

Elektrochemische Synthese von Pyrazolinen und Pyrazolen via [3+2] dipolarer Cycloaddition

“…[14][15][16] Darüber hinaus ist Pyrazolin 2 ein wichtiges Zwischenprodukt bei der Synthese verschiedener potenter Cannabinoid-CB 1 -Rezeptorantagonisten, die bei der Behandlung von Fettleibigkeit und damit verbundener Risiken sowie von Krebs und entzündlichen Prozessen und deren Folgen eingesetzt werden. [17,18] Konventionell können Pyrazole und Pyrazoline durch Kondensation von 1,3-Diketonen oder α,β-ungesättigten Ketonen [19] mit Hydrazinen synthetisiert werden. [3+2]-Dipolare Cycloadditionen von Nitriliminen und Alkenen oder Alkinen ermöglichen ebenfalls den Zugang zu diesen Verbindungen, [20,21] wobei die Nitrilimine meist durch Abspaltung von Chlorwasserstoff aus Hydrazonoylchloriden gebildet werden (Schema 1, oben).…”