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Molecules 2018, 23(2), 297; https://doi.org/10.3390/molecules23020297

Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds

1
Department of Pharmaceutical Chemistry, College of Pharmacy, Aljouf University, Sakaka 2014, Aljouf Province, Saudi Arabia
2
Department of Pharmacology, College of Pharmacy, Aljouf University, Sakaka 2014, Aljouf Province, Saudi Arabia
3
Department of Pharmacology, Anwarul Uloom College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad 500001, Telangana, India
4
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
5
Department of Biotechnology & Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62574, Egypt
6
Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea
7
Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
8
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Alshaheed Shehata Ahmed Hegazy St., Beni-Suef 62574, Egypt
9
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
10
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
11
Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology & Information, 11571 Cairo, Egypt
*
Authors to whom correspondence should be addressed.
Received: 13 December 2017 / Revised: 1 January 2018 / Accepted: 22 January 2018 / Published: 31 January 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5an were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5ae with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines. View Full-Text
Keywords: cancer; cell line; synthesis; urea derivatives; antiproliferative; activity cancer; cell line; synthesis; urea derivatives; antiproliferative; activity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Al-Sanea, M.M.; Ali Khan, M.S.; Abdelazem, A.Z.; Lee, S.H.; Mok, P.L.; Gamal, M.; Shaker, M.E.; Afzal, M.; Youssif, B.G.M.; Omar, N.N. Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds. Molecules 2018, 23, 297.

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