The Crystal Structure of 2-Amino-4-(2,3-Dichlorophenyl)-6-Methoxy-4<i>H</i>-Benzo[<i>h</i>]chromene-3-Carbonitrile: Antitumor and Tyrosine Kinase Receptor Inhibition Mechanism Studies
Ahmed M. El-Agrody,
Ahmed M. Fouda,
Hany M. Mohamed,
Mohammed Y. Alshahrani,
Hazem A. Ghabbour,
Abd El-Galil E. Amr,
Rawda M. Okasha,
Ahmed M. Naglah,
Abdulrahman A. Almehizia,
Ahmed A. Elhenawy
Affiliations
Ahmed M. El-Agrody
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
Ahmed M. Fouda
Chemistry Department, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia
Hany M. Mohamed
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
Mohammed Y. Alshahrani
Department of Clinical Laboratory Science, College of Applied Medical Science, King Khalid University, Abha 61413, Saudi Arabia
Hazem A. Ghabbour
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt
Abd El-Galil E. Amr
Pharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Rawda M. Okasha
Chemistry Department, Faculty of Science, Taibah University, Medina 30002, Saudi Arabia
Ahmed M. Naglah
Pharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Abdulrahman A. Almehizia
Pharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Ahmed A. Elhenawy
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
The target compound, 2-amino-4-(2,3-dichlorophenyl)-6-methoxy-4H-benzo[h]chromene -3-carbonitrile (4), was synthesized via the reaction of 4-methoxynaphthalen-1-ol (1), 2,3-dichlorobenzaldehyde (2), and malononitrile (3) in an ethanolic piperidine solution under microwave irradiation. The synthesized β-enaminonitrile derivative (4) was characterized by spectral data and X-ray diffraction. The in vitro anti-proliferative profile was conducted against five cancer cell lines and was assessed for compound 4, which revealed strong and selective cytotoxic potency. This derivative showed promising inhibition efficacy against the EGFR and VEGFR-2 kinases in comparison to Sorafenib as a reference inhibitor. Lastly, the docking analysis into the EGFR and VEGFR-2 active sites was performed to clarify our biological findings.
