TY - JOUR
T1 - Multicomponent synthesis, cytotoxicity, and computational studies of novel imidazopyridazine-based N-phenylbenzamides
AU - Malik, M. Shaheer
AU - Alsantali, Reem A.
AU - Alzahrani, Abdullah Y.A.
AU - Jamal, Qazi Mohammad Sajid
AU - Hussein, Essam M.
AU - Alfaidi, Khalid A.
AU - Al-Rooqi, Munirah M.
AU - Obaid, Rami J.
AU - Alsharif, Meshari A.
AU - Adil, Syed Farooq
AU - Jassas, Rabab S.
AU - Moussa, Ziad
AU - Ahmed, Saleh A.
N1 - Funding Information:
The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through the Small Research Project under grant number (RGP.1/124/42). The authors would like to acknowledge the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant code: 22UQU4320545DSR06. The authors would like to extend their sincere appreciation to Taif University Researchers Supporting Project number (TURSP-2020/312), Taif University, Taif, Saudi Arabia.
Publisher Copyright:
© 2022 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - A one-pot multicomponent synthesis and application of new imidazopyridazine based N-phenylbenzamides is described. An atom-economical method involving dimethyl phthalate, substituted anilines, and pyridazine-4,5-diamine provided the desired compounds in 120–150 min with 80–85% yield. The reaction was catalyzed with phosphoric acid, and glycerol was used as a safer, greener solvent. Anticancer evaluation against selected cancer cell lines revealed that compound 4e was the most active from the series and exhibited IC50 values below 9.1 µM. Compounds 4h and 4d also displayed good and comparable IC50 values (10.2–12.1 µM). Molecular docking and molecular dynamic studies showed that compound 4e exhibit good binding affinity and stable complex formation with ABL1-kinase protein, respectively. Additional computational predictions such as ADME and drug-likeness demonstrated the potential of the new benzamides as leads for further development.
AB - A one-pot multicomponent synthesis and application of new imidazopyridazine based N-phenylbenzamides is described. An atom-economical method involving dimethyl phthalate, substituted anilines, and pyridazine-4,5-diamine provided the desired compounds in 120–150 min with 80–85% yield. The reaction was catalyzed with phosphoric acid, and glycerol was used as a safer, greener solvent. Anticancer evaluation against selected cancer cell lines revealed that compound 4e was the most active from the series and exhibited IC50 values below 9.1 µM. Compounds 4h and 4d also displayed good and comparable IC50 values (10.2–12.1 µM). Molecular docking and molecular dynamic studies showed that compound 4e exhibit good binding affinity and stable complex formation with ABL1-kinase protein, respectively. Additional computational predictions such as ADME and drug-likeness demonstrated the potential of the new benzamides as leads for further development.
KW - Computational studies
KW - Cytotoxicity
KW - Imidazopyridazine
KW - Multicomponent reaction
KW - N-Phenylbenzamide
UR - http://www.scopus.com/inward/record.url?scp=85125949198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125949198&partnerID=8YFLogxK
U2 - 10.1016/j.jscs.2022.101449
DO - 10.1016/j.jscs.2022.101449
M3 - Article
AN - SCOPUS:85125949198
SN - 1319-6103
VL - 26
JO - Journal of Saudi Chemical Society
JF - Journal of Saudi Chemical Society
IS - 3
M1 - 101449
ER -