Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H)-Ones

Emmanuel Ndubuisi Agbo; Tshepiso Jan Makhafola; Yee Siew Choong; Malose Jack Mphahlele; Ponnadurai Ramasami

doi:10.3390/molecules21010028

Synthesis, Biological Evaluation and Molecular Docking Studies of 6-Aryl-2-Styrylquinazolin-4(3H)-Ones

Molecules. 2015 Dec 25;21(1):E28. doi: 10.3390/molecules21010028.

Authors

Emmanuel Ndubuisi Agbo¹, Tshepiso Jan Makhafola², Yee Siew Choong³, Malose Jack Mphahlele⁴, Ponnadurai Ramasami⁵

Affiliations

¹ Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, P. O. Box 392, Pretoria 0003, South Africa. tagboen@unisa.ac.za.
² Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa. makhat@unisa.ac.za.
³ Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia. yeesiew@usm.my.
⁴ Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, P. O. Box 392, Pretoria 0003, South Africa. mphahmj@unisa.ac.za.
⁵ Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius. ramchemi@intnet.mu.

Abstract

Suzuki-Miyaura cross-coupling of 6-bromo-2-styrylquinazolin-4(3H)-ones with arylboronic acids afforded a series of novel 6-aryl-2-styrylquinazolin-4(3H)-ones. These compounds were evaluated for potential anticancer properties against the human renal (TK-10), melanoma (UACC-62) and breast cancer (MCF-7) cell lines. Their antimicrobial properties were also evaluated against six Gram-positive and four Gram-negative bacteria, as well as two strains of fungi. Molecular docking studies (in silico) were conducted on compounds 5a, b, d and 6a, b, d-f to recognize the hypothetical binding motif of the title compounds within the active site of the dihydrofolate reductase and thymidylate synthase enzymes.

Keywords: 6-aryl-2-styrylquinazolin-4(3H)-ones; 6-bromo-2-styrylquinazolin-4(3H)-ones; Suzuki-Miyaura cross-coupling; antimicrobial activity; docking studies; in vitro cytotoxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents / chemical synthesis*
Anti-Infective Agents / chemistry
Anti-Infective Agents / pharmacology
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Catalytic Domain / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Humans
MCF-7 Cells
Models, Molecular
Molecular Docking Simulation
Quinazolines / chemical synthesis*
Quinazolines / chemistry
Quinazolines / pharmacology*
Tetrahydrofolate Dehydrogenase / chemistry
Tetrahydrofolate Dehydrogenase / metabolism
Thymidylate Synthase / chemistry
Thymidylate Synthase / metabolism

Substances

Anti-Infective Agents
Antineoplastic Agents
Quinazolines
Tetrahydrofolate Dehydrogenase
Thymidylate Synthase