Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines

A new series of flurbiprofen derivatives containing thiosemicarbazide moiety (3-7) was synthesized from flurbiprofen as parent nucleus by esterification, hydrazide formation, and heating with different aryl isothiocyanate substituents, respectively. Flurbiprofen was also treated with thiosemica...

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Autores principales:	Kasim S. Hmood, Ammar A. Razzak Mahmood Kubba, Redha I Al-bayati, Abdulrahman M. Saleh
Formato:	article
Lenguaje:	EN
Publicado:	Universitas Gadjah Mada 2021
Materias:	thiosemicarbazide anticancer activity thiourea aryl isothiocyanate high content screening Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/4626fbc3c69f418ca266989d595e3495
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spelling	oai:doaj.org-article:4626fbc3c69f418ca266989d595e34952021-11-15T06:08:47ZSynthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines2338-94272338-948610.22146/ijp.730https://doaj.org/article/4626fbc3c69f418ca266989d595e34952021-01-01T00:00:00Zhttps://jurnal.ugm.ac.id/v3/IJP/article/view/730https://doaj.org/toc/2338-9427https://doaj.org/toc/2338-9486A new series of flurbiprofen derivatives containing thiosemicarbazide moiety (3-7) was synthesized from flurbiprofen as parent nucleus by esterification, hydrazide formation, and heating with different aryl isothiocyanate substituents, respectively. Flurbiprofen was also treated with thiosemicarbazide in the presence POCl3 as a catalyst, to produce 1,3,4 -thiadiazole -2-amine (8). Treatment of (8) with different aryl isothiocyanates produced thiourea derivatives (9-12). Also, the reaction of (8) with different benzoyl chloride substituents produced benzamide compounds (13-15). Eventually , treatment of (8) with ethyl acetoacetate(EAA) produced [1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one (16) .The new compounds were characterized by spectroscopic techniques :FTIR, 1HNMR, and CHNS analysis. A molecular docking study for the synthesized compounds (3-16), against the Vascular Endothelial Growth Factor receptor (VEGFR-2) was applied and it indicated that compounds 4,7,13, and 15,exhibited the optimum binding energy of -6.77, -6.12,-6.68, and -6.43 kcal/mol, respectively. Target compounds were also assessed for their in vitro anticancer effects in a cell-line study. All of the compounds tested showed the most plausible anticancer activity, compared to a positive control(Sorafenib), using in vitro MTT cytotoxic assay ,against human breast tumor (MCF-7), and normal WRL-68 cell line. The in vitro results revealed that compounds 4,5,10,11,13, and 15 exhibited the highest inhibitory activity at their IC50 concentrations, against MCF-7 cell lines, as follows (122.7,113.9,95,7. 109.1,40.32 and 112.29µg/mL, respectively. While their cytotoxic effect against normal WRL-68 cell line at their IC50 concentrations, as follow 210.2, 181.3 ,151.7,278.7,80.28, and 236 µg/mL, respectively, therefore, such compounds were considered more selective toward MCF-7 than normal WRL-68,and their selectivity index (SI): 1.71,1.59,1.59 ,2.55 ,1.99 , and 2.10,respectively . Among the synthesized compounds, the compound 15 was chosen to screen its effect in vitro through multi-parameter cytotoxic assay against MCF-7 breast cancer implemented in High Content Screening (ArrayScan XTI, Thermo Scientific),which could be taken in consideration as a starting point for the development of new anticancer drugsKasim S. HmoodAmmar A. Razzak Mahmood KubbaRedha I Al-bayatiAbdulrahman M. SalehUniversitas Gadjah Madaarticlethiosemicarbazideanticancer activitythioureaaryl isothiocyanatehigh content screeningPharmacy and materia medicaRS1-441ENIndonesian Journal of Pharmacy, Pp 17-34 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thiosemicarbazide anticancer activity thiourea aryl isothiocyanate high content screening Pharmacy and materia medica RS1-441
spellingShingle	thiosemicarbazide anticancer activity thiourea aryl isothiocyanate high content screening Pharmacy and materia medica RS1-441 Kasim S. Hmood Ammar A. Razzak Mahmood Kubba Redha I Al-bayati Abdulrahman M. Saleh Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
description	A new series of flurbiprofen derivatives containing thiosemicarbazide moiety (3-7) was synthesized from flurbiprofen as parent nucleus by esterification, hydrazide formation, and heating with different aryl isothiocyanate substituents, respectively. Flurbiprofen was also treated with thiosemicarbazide in the presence POCl3 as a catalyst, to produce 1,3,4 -thiadiazole -2-amine (8). Treatment of (8) with different aryl isothiocyanates produced thiourea derivatives (9-12). Also, the reaction of (8) with different benzoyl chloride substituents produced benzamide compounds (13-15). Eventually , treatment of (8) with ethyl acetoacetate(EAA) produced [1,3,4]thiadiazolo[3,2-a]pyrimidin-7-one (16) .The new compounds were characterized by spectroscopic techniques :FTIR, 1HNMR, and CHNS analysis. A molecular docking study for the synthesized compounds (3-16), against the Vascular Endothelial Growth Factor receptor (VEGFR-2) was applied and it indicated that compounds 4,7,13, and 15,exhibited the optimum binding energy of -6.77, -6.12,-6.68, and -6.43 kcal/mol, respectively. Target compounds were also assessed for their in vitro anticancer effects in a cell-line study. All of the compounds tested showed the most plausible anticancer activity, compared to a positive control(Sorafenib), using in vitro MTT cytotoxic assay ,against human breast tumor (MCF-7), and normal WRL-68 cell line. The in vitro results revealed that compounds 4,5,10,11,13, and 15 exhibited the highest inhibitory activity at their IC50 concentrations, against MCF-7 cell lines, as follows (122.7,113.9,95,7. 109.1,40.32 and 112.29µg/mL, respectively. While their cytotoxic effect against normal WRL-68 cell line at their IC50 concentrations, as follow 210.2, 181.3 ,151.7,278.7,80.28, and 236 µg/mL, respectively, therefore, such compounds were considered more selective toward MCF-7 than normal WRL-68,and their selectivity index (SI): 1.71,1.59,1.59 ,2.55 ,1.99 , and 2.10,respectively . Among the synthesized compounds, the compound 15 was chosen to screen its effect in vitro through multi-parameter cytotoxic assay against MCF-7 breast cancer implemented in High Content Screening (ArrayScan XTI, Thermo Scientific),which could be taken in consideration as a starting point for the development of new anticancer drugs
format	article
author	Kasim S. Hmood Ammar A. Razzak Mahmood Kubba Redha I Al-bayati Abdulrahman M. Saleh
author_facet	Kasim S. Hmood Ammar A. Razzak Mahmood Kubba Redha I Al-bayati Abdulrahman M. Saleh
author_sort	Kasim S. Hmood
title	Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
title_short	Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
title_full	Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
title_fullStr	Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
title_full_unstemmed	Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines
title_sort	synthesis, and anti-tumor evaluation of some new flurbiprofen derivatives against mcf-7 and wrl-68 cell lines
publisher	Universitas Gadjah Mada
publishDate	2021
url	https://doaj.org/article/4626fbc3c69f418ca266989d595e3495
work_keys_str_mv	AT kasimshmood synthesisandantitumorevaluationofsomenewflurbiprofenderivativesagainstmcf7andwrl68celllines AT ammararazzakmahmoodkubba synthesisandantitumorevaluationofsomenewflurbiprofenderivativesagainstmcf7andwrl68celllines AT redhaialbayati synthesisandantitumorevaluationofsomenewflurbiprofenderivativesagainstmcf7andwrl68celllines AT abdulrahmanmsaleh synthesisandantitumorevaluationofsomenewflurbiprofenderivativesagainstmcf7andwrl68celllines
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Synthesis, and Anti-Tumor Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines

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