Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties.
In our endeavor towards the development of potent anticancer agents, two different sets of biphenylurea-indolinone conjugates, 5a-s and 8a,b were synthesized. The in vitro cytotoxicity of the synthesized compounds was examined in two human cancer cell lines, namely MCF-7 breast cancer and PC-3 prostate cancer cells using the sulforhodamine B (SRB) colorimetric assay. In particular, the MCF-7 cancer cell line was more susceptible to the synthesized compounds. Compound 5o (IC50 = 1.04 ± 0.10 μM) emerged as the most active member in this study against MCF-7, with 7-fold increased activity compared to the reference drug, doxorubicin (IC50 = 7.30 ± 0.84 μM). Compounds 5l, 5q and 8b also exhibited superior cytotoxic activity against MCF-7 with IC50 values of 1.93 ± 0.17, 3.87 ± 0.31 and 4.66 ± 0.42 μM, respectively. All of the tested compounds were filtered according to the Lipinski and Veber rules and all of them passed the filters. Additionally, several ADME descriptors for the synthesized compounds 5a-s and 8a,b were predicted via a theoretical kinetic study performed using the Discovery Studio 2.5 software.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. wagdy2000@gmail.com.
Wagdy M
WM
Eldehna
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. ph.fares@yahoo.com.|School of Chemistry, University of Wollongong, Wollongong 2522, New South Wales, Australia. ph.fares@yahoo.com.
Mohamed
M
Fares
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt. hany.s.ibrahim@gmail.com.
Hany S
HS
Ibrahim
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Muhammad.alsherbiny@pharma.cu.edu.eg.
Muhammad A
MA
Alsherbiny
Department of Pharmacology and Toxicology, Faculty of Pharmacy, British University in Egypt, Cairo 11562, Egypt. mohamed.aly@bue.edu.eg.|Department of Biology, The American University in Cairo, New Cairo 11835, Egypt. mohamed.aly@bue.edu.eg.
Mohamed H
MH
Aly
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.
Hazem A
HA
Ghabbour
Department of Applied Organic Chemistry, National Research Center, Dokki, Giza 12622, Egypt. hatem_741@yahoo.com.
Hatem A
HA
Abdel-Aziz
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D061986:MCF-7 Cells; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012235:Rhodamines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014508:Urea / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; D007211:Indoles; D012235:Rhodamines; C456900:indolin-2-one; C022027:lissamine rhodamine B; D004317:Doxorubicin; D014508:Urea
ADME; biphenylurea; cytotoxic activity; indolinone