title: Synthesis of new spirooxindole-pyrrolothiazole derivatives: Anti-cancer activity and molecular docking.
abstract: The 1,3-dipolar cycloadditions of an azomethine ylide generated from isatin and thiazolidinecarboxylic acid to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded new di-spiro heterocycles incorporating pyrrolidine and oxindole rings in quantitative yields and chemo-, regio-, and stereoselectively. The newly synthesized compounds were characterized using spectroscopic techniques. Furthermore, the molecular structures of 4a, 4e, and 4n were confirmed by X-ray crystallography. These newly synthesized compounds were screened for their in vitro activity against breast cancer cell line MCF-7 and K562-leukemia. 4k was found to be the most potent compound of this series in targeting MCF-7 breast cancer cells and K562-leukemia, with IC50values of 15.32±0.02 and 14.74±0.7μM, respectively. The molecular studies of the synthesized compounds were investigated.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Gehad
authors.initials: G
authors.lastname: Lotfy
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Said
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
authors.forename: El Sayed H
authors.initials: ESH
authors.lastname: El Ashry
authors.affiliation: Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt.
authors.forename: El Sayed H
authors.initials: ESH
authors.lastname: El Tamany
authors.affiliation: Stem Cell Therapy & Tissue Re-engineering Program, King Faisal Specialized Hospital and Research Center, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Dhfyan
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Abdel Aziz
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: ambarakat@ksu.edu.sa.
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D013141:Spiro Compounds; D013844:Thiazoles
keywords: 1,3-Dipolar cycloaddition; Atom economy; Azomethine ylide; Breast cancer; Leukemia; Molecular docking; Oxindole; Pyrrolidine; Spirocyclohexanone