Przewalcyrones A-F, epoxychromene-containing polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum przewalskii Maxim

• Published in: Organic & biomolecular chemistry Vol. 17; no. 35; pp. 8234 - 8242
• Main Authors: Duan, Yulin, Xie, Shuangshuang, Guo, Yi, Qiao, Yuben, Shi, Zhengyi, Tao, Li, Deng, Mengyi, Cao, Yunfang, Xue, Yongbo, Qi, Changxing, Zhang, Yonghui
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.09.2019; Royal Society of Chemistry
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; CD28 antigen; CD3 antigen; Cell Proliferation - drug effects; Chemistry; Chemistry, Organic; Circular dichroism; Crystallography; Dichroism; Dose-Response Relationship, Drug; Healthy Volunteers; Humans; Hypericum; Hypericum - chemistry; Immunosuppressive agents; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - isolation & purification; Immunosuppressive Agents - pharmacology; Leukocytes, Mononuclear - drug effects; Lymphocytes; Lymphocytes T; Molecular Conformation; Monoclonal antibodies; NMR; Nuclear magnetic resonance; Organic chemistry; Phloroglucinol - analogs & derivatives; Phloroglucinol - chemistry; Phloroglucinol - pharmacology; Physical Sciences; Science & Technology; Stereoisomerism; Structure-Activity Relationship; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; AMINO-ACID-METABOLISM; DERIVATIVES
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c9ob01500k

Chemical investigation of the extracts of the aerial parts of Hypericum przewalskii Maxim. resulted in the isolation and identification of six new epoxychromene-containing polycyclic polyprenylated acylphloroglucinols (PPAPs), named przewalcyrones A-F (1-6), and one known analogue (7). All of the structures were determined based on extensive spectroscopic analyses, X-ray crystallographic analysis, modified Mosher's method, [Rh-2(OCOCF3)(4)]-induced ECD, and electronic circular dichroism (ECD) comparison. Structurally, przewalcyrones A-F represent the first examples of PPAPs containing an unexpected 8,8-dimethyl-3,9-epoxychromene moiety. All these compounds were evaluated for the immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibody (mAb)-stimulated human T cells. Among them, przewalcyrones C and D exhibited potential in vitro immunosuppressive activity, with IC50 values of (5.01 +/- 0.52) mu M and (5.26 +/- 0.56) mu M, respectively, highlighting those compounds as a promising starting point for the development of new immunosuppressive agents.