Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives

The current study aimed to design and synthesize a novel series of fluorophenyl-isoxazole-carboxamide derivatives and evaluate their antiproliferative activities. Anticancer activities of the novel compounds were evaluated by MTS assay against four cancer cell lines, including liver (Hep3B, HepG2),...

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Autores principales:	Hawash Mohammed, Jaradat Nidal, Abualhasan Murad, Amer Johnny, Levent Serkan, Issa Shahd, Ibrahim Sameeha, Ayaseh Aseel, Shtayeh Tahrir, Mousa Ahmed
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	isoxazole anticancer hep3b doxorubicin Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1e00ebae391745c98a4cd8fbdb12fd31
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spelling	oai:doaj.org-article:1e00ebae391745c98a4cd8fbdb12fd312021-12-05T14:10:44ZSynthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives2391-542010.1515/chem-2021-0078https://doaj.org/article/1e00ebae391745c98a4cd8fbdb12fd312021-08-01T00:00:00Zhttps://doi.org/10.1515/chem-2021-0078https://doaj.org/toc/2391-5420The current study aimed to design and synthesize a novel series of fluorophenyl-isoxazole-carboxamide derivatives and evaluate their antiproliferative activities. Anticancer activities of the novel compounds were evaluated by MTS assay against four cancer cell lines, including liver (Hep3B, HepG2), cervical (HeLa), and breast (MCF-7), and α-fetoprotein tumor marker, cell cycle analysis, and annexin V tests. Chemo-informatics analysis showed that all synthesized derivatives 2a–2f obeyed Lipinski’s rule. Compound 2f was the most potent compound against Hep3B and Hep-G2 cancer cell lines with IC50 values of 5.76 and 34.64 µg/mL, respectively. Moreover, compounds 2a–2c and 2e showed potent inhibitory activity against Hep3B with an IC50 value range of 7.66–11.60 µg/mL. Hep3B secretions of α-fetoprotein (α-FP) results showed that compound 2f reduced the secretion of Hep3B to 168.33 ng/mL and compound 2d reduced the secretion to value approximately 598.33 ng/mL, in comparison with untreated cells’ value of 1116.67 ng/mL. Furthermore, cell cycle analysis showed that the 2f compound induced arrest in the G2-M phase in 6.73% of the total cells and that was lower than the activity of the positive control doxorubicin (7.4%). Moreover, 2b and 2f compounds reduced the necrosis rate of Hep3B to 4-folds and shifted the cells to apoptosis.Hawash MohammedJaradat NidalAbualhasan MuradAmer JohnnyLevent SerkanIssa ShahdIbrahim SameehaAyaseh AseelShtayeh TahrirMousa AhmedDe Gruyterarticleisoxazoleanticancerhep3bdoxorubicinChemistryQD1-999ENOpen Chemistry, Vol 19, Iss 1, Pp 855-863 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	isoxazole anticancer hep3b doxorubicin Chemistry QD1-999
spellingShingle	isoxazole anticancer hep3b doxorubicin Chemistry QD1-999 Hawash Mohammed Jaradat Nidal Abualhasan Murad Amer Johnny Levent Serkan Issa Shahd Ibrahim Sameeha Ayaseh Aseel Shtayeh Tahrir Mousa Ahmed Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
description	The current study aimed to design and synthesize a novel series of fluorophenyl-isoxazole-carboxamide derivatives and evaluate their antiproliferative activities. Anticancer activities of the novel compounds were evaluated by MTS assay against four cancer cell lines, including liver (Hep3B, HepG2), cervical (HeLa), and breast (MCF-7), and α-fetoprotein tumor marker, cell cycle analysis, and annexin V tests. Chemo-informatics analysis showed that all synthesized derivatives 2a–2f obeyed Lipinski’s rule. Compound 2f was the most potent compound against Hep3B and Hep-G2 cancer cell lines with IC50 values of 5.76 and 34.64 µg/mL, respectively. Moreover, compounds 2a–2c and 2e showed potent inhibitory activity against Hep3B with an IC50 value range of 7.66–11.60 µg/mL. Hep3B secretions of α-fetoprotein (α-FP) results showed that compound 2f reduced the secretion of Hep3B to 168.33 ng/mL and compound 2d reduced the secretion to value approximately 598.33 ng/mL, in comparison with untreated cells’ value of 1116.67 ng/mL. Furthermore, cell cycle analysis showed that the 2f compound induced arrest in the G2-M phase in 6.73% of the total cells and that was lower than the activity of the positive control doxorubicin (7.4%). Moreover, 2b and 2f compounds reduced the necrosis rate of Hep3B to 4-folds and shifted the cells to apoptosis.
format	article
author	Hawash Mohammed Jaradat Nidal Abualhasan Murad Amer Johnny Levent Serkan Issa Shahd Ibrahim Sameeha Ayaseh Aseel Shtayeh Tahrir Mousa Ahmed
author_facet	Hawash Mohammed Jaradat Nidal Abualhasan Murad Amer Johnny Levent Serkan Issa Shahd Ibrahim Sameeha Ayaseh Aseel Shtayeh Tahrir Mousa Ahmed
author_sort	Hawash Mohammed
title	Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
title_short	Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
title_full	Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
title_fullStr	Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
title_full_unstemmed	Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
title_sort	synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/1e00ebae391745c98a4cd8fbdb12fd31
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Synthesis, chemo-informatics, and anticancer evaluation of fluorophenyl-isoxazole derivatives

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