PTSA-induced synthesis, <i>in silico</i> and nano study of novel ethylquinolin–thiazolo–triazole in cervical cancer
Creators: name: Sonker, Priyanka
name: Tamang, Rupen
name: Mehata, Abhishesh K
name: Nidhar, Manisha
name: Sharma, Vishal P
name: Kumar, Vipin
name: Muthu, Madaswamy S
name: Koch, Biplob
name: Tewari, Ashish K
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Biochemistry
Space Science
Medicine
Cell Biology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Cancer
Hematology

description: <b>Aim:</b> p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin–thiazolo–triazole derivatives was performed using green chemistry. <b>Materials &amp; methods:</b> Development of a nanoconjugate drug-delivery system of ethylquinolin–thiazolo–triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and <i>in vitro</i> drug release assay. The effect of <b>3a</b> nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. <b>Results &amp; discussion:</b> The <b>3a</b> nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, <i>in silico</i> studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. <b>Conclusion:</b> The <b>3a</b> nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer. Green chemistry was used to create (E)-2-(2-((2-chloroquinolin-3-yl)methylene)hydrazineyl)-4-phenylthiazole derivatives through p-Toluenesulfonic acid-(PTSA) and grinding. Nuclear magnetic resonance and high-resolution mass spectrometry were used to characterize the derivatives. Furthermore, molecular docking experiments were carried out, and the absorption, distribution, metabolism, elimination and toxicity and drug-likeness were predicted. D-α-tocopheryl polyethylene glycol succinate was used to create a nanoconjugate drug-delivery system with the synthetic chemical (2-chloro-8-ethylquinolin-3-yl)-5-phenyl-1,7a-dihydrothiazolo[2,3-c][1,2,4] triazole, which was then characterized by transmission electron microscopy, scanning electron microscopy and an <i>in vitro</i> drug release experiment. p-Toluenesulfonic acid- and grinding-induced synthesis of (E)-2-(2-((2-chloroquinolin-3-yl) methylene) hydrazineyl)-4-phenylthiazole derivatives was performed through green chemistry. Characterization of the derivatives was performed through nuclear magnetic resonance, high-resolution mass spectrometry, atomic force microscopy, dynamic light scattering and transmission electron microscopy. In addition, molecular docking studies were conducted and the absorption, distribution, metabolism, elimination and toxicity properties and drug-likeness were predicted. Development of a nanoconjugate drug-delivery system with the selected synthetic compound (2-chloro-8-ethylquinolin-3-yl)-5-phenyl-1,7a-dihydrothiazolo[2,3-c][1,2,4] triazole was carried out with TPGS and the nanoformulation was further characterized by transmission electron microscopy, scanning electron microscopy and <i>in vitro</i> drug release assay. The effect of <b>3a–</b>NP was assessed against cervical cancer cell line (HeLa) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the effects on apoptosis were also determined. <b>3a–</b>NP IC<sub>50</sub> values demonstrated extremely high activity against a cervical carcinoma cell line. Fluorescence microscopy and flow cytometry analysis demonstrated that <b>3a–</b>NP triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing the cellular uptake of micelles. Furthermore, <i>in silico</i> studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties, bioavailability and potent activity toward the enzyme tyrosine protein kinase. Our study demonstrates that <b>3a–</b>NP may enhance the therapeutic potential and holds promise for targeted drug delivery against cervical cancer.