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Molecules 2018, 23(6), 1420; https://doi.org/10.3390/molecules23061420

Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation

1
Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah 27272, UAE
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt
3
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, OX1 3TA Oxford, UK
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt
5
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt
6
School of Chemistry, University of Wollongong, Wollongong 2522, New South Wales, Australia
7
The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11759, Egypt
8
Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt
*
Author to whom correspondence should be addressed.
Received: 17 May 2018 / Revised: 7 June 2018 / Accepted: 8 June 2018 / Published: 12 June 2018
(This article belongs to the Section Medicinal Chemistry)
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Abstract

In connection with our research program on the development of new isatin-based anticancer candidates, herein we report the synthesis of two novel series of thiazolidinone-isatin conjugates (4an) and thiazolo[3,2-a]benzimidazolone-isatin conjugates (7ad), and in vitro evaluation of their antiproliferative activity towards two breast cancer cell lines; triple negative MDA-MB-231, and MCF-7. Compounds 4m and 7b emerged as the most active congeners against MDA-MB-231 cells (IC50 = 7.6 ± 0.5 and 13.2 ± 1.1 µM, respectively). Compounds 4m and 7b were able to provoke apoptosis in MDA-MB-231 cells, evidenced by the up-regulation of Bax and down-regulation of Bcl-2, besides boosting caspase-3 levels. Hybrid 4m induced a fourfold increase in the percentage of cells at Sub-G1, with concurrent arrest in G2-M phase by 2.5-folds. Furthermore, hybrid 4m resulted in a sixfold increase in the percentage of annexin V-FITC positive apoptotic MDA-MB-231 cells as compared with the control. Moreover, the cytotoxic activities of the active conjugates were assessed towards two nontumorigenic cell lines (breast MCF-10A and lung WI-38) where both conjugates 4m and 7b displayed mean tumor selectivity index: 9.6 and 13.9, respectively. Finally, several ADME descriptors were predicted for the active conjugates via a theoretical kinetic study. View Full-Text
Keywords: triple-negative breast cancer; isatin-thiazolidinone hybrids; anticancer; apoptosis; QSAR triple-negative breast cancer; isatin-thiazolidinone hybrids; anticancer; apoptosis; QSAR
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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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El-Naggar, M.; Eldehna, W.M.; Almahli, H.; Elgez, A.; Fares, M.; Elaasser, M.M.; Abdel-Aziz, H.A. Novel Thiazolidinone/Thiazolo[3,2-a]Benzimidazolone-Isatin Conjugates as Apoptotic Anti-proliferative Agents Towards Breast Cancer: One-Pot Synthesis and In Vitro Biological Evaluation. Molecules 2018, 23, 1420.

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