Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria

Guang Xian Pang; Chao Niu; Nuramina Mamat; Haji Akber Aisa

doi:10.1016/j.bmcl.2017.04.039

Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria

Bioorg Med Chem Lett. 2017 Jun 15;27(12):2674-2677. doi: 10.1016/j.bmcl.2017.04.039. Epub 2017 Apr 14.

Authors

Guang Xian Pang¹, Chao Niu², Nuramina Mamat¹, Haji Akber Aisa³

Affiliations

¹ Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; University of Chinese Academy of Sciences, 19 A Yuquan Rd, Beijing 100049, China.
² Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
³ Key Laboratory of Plant Resources and Chemistry of Arid Zone, Chinese Academy of Sciences, Urumqi 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China. Electronic address: haji@ms.xjb.ac.cn.

PMID: 28476568
DOI: 10.1016/j.bmcl.2017.04.039

Abstract

A novel series of coumarin derivatives 6a-o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b-f, 6j-o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e-f and 6l-m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship.

Keywords: Antimicrobial activity; Coumarin derivatives; Melanin synthesis; SAR; Vitiligo.

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Candida albicans / drug effects
Candida albicans / growth & development
Cell Line, Tumor
Cell Survival / drug effects
Coumarins / chemical synthesis
Coumarins / chemistry
Coumarins / pharmacology*
Dose-Response Relationship, Drug
Escherichia coli / drug effects
Escherichia coli / growth & development
Humans
Isoxazoles / chemistry
Isoxazoles / pharmacology*
Melanins / biosynthesis*
Microbial Sensitivity Tests
Molecular Structure
Staphylococcus aureus / drug effects
Staphylococcus aureus / growth & development
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Coumarins
Isoxazoles
Melanins
coumarin