Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

Yiming Xu; Lichuan Wu; Hang Dai; Mingyan Gao; Haroon Ur Rashid; Haodong Wang; Peng Xie; Xu Liu; Jun Jiang; Lisheng Wang

doi:10.3390/molecules22111967

Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

Molecules. 2017 Nov 14;22(11):1967. doi: 10.3390/molecules22111967.

Authors

Yiming Xu¹, Lichuan Wu^{2

3}, Hang Dai⁴, Mingyan Gao⁵, Haroon Ur Rashid^{6

7}, Haodong Wang⁸, Peng Xie⁹, Xu Liu¹⁰, Jun Jiang¹¹, Lisheng Wang¹²

Affiliations

¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
² Medicinal College, Guangxi University, Nanning 530004, China. [email protected].
³ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University; Guilin 541000, China. [email protected].
⁴ College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530004, China. [email protected].
⁵ College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530004, China. [email protected].
⁶ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
⁷ Department of Chemistry, Sarhad University of Science & Information Technology, Peshawar, Khyber Pakhtunkhwa 25120, Pakistan. [email protected].
⁸ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
⁹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
¹⁰ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
¹¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].
¹² School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China. [email protected].

Abstract

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

Keywords: anticancer activity; chalcone; derivatives; molecular docking; sophoridine.

MeSH terms

Alkaloids / chemical synthesis
Alkaloids / chemistry*
Alkaloids / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Chemistry Techniques, Synthetic*
DNA / chemistry
Dose-Response Relationship, Drug
Drug Design*
Humans
Matrines
Models, Molecular*
Molecular Conformation
Molecular Docking Simulation
Molecular Structure
Quinolizines / chemical synthesis
Quinolizines / chemistry*
Quinolizines / pharmacology*
Structure-Activity Relationship

Substances

Alkaloids
Antineoplastic Agents
Quinolizines
DNA
Matrines