Laevifins A-G, clerodane diterpenoids from the Bark of Croton oblongus Burm.f

Ahmad Nazif Aziz; Nor Hadiani Ismail; Siti Nadiah Abdul Halim; Chung Yeng Looi; El Hassane Anouar; Moses K Langat; Dulcie Mulholland; Khalijah Awang

doi:10.1016/j.phytochem.2018.10.002

Laevifins A-G, clerodane diterpenoids from the Bark of Croton oblongus Burm.f

Phytochemistry. 2018 Dec:156:193-200. doi: 10.1016/j.phytochem.2018.10.002. Epub 2018 Oct 10.

Authors

Ahmad Nazif Aziz¹, Nor Hadiani Ismail², Siti Nadiah Abdul Halim³, Chung Yeng Looi⁴, El Hassane Anouar⁵, Moses K Langat⁶, Dulcie Mulholland⁶, Khalijah Awang³

Affiliations

¹ School of Fundamental Science, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Malaysia; Atta-ur-Rahman Institute for Natural Products Discovery, Level 9, FF3, Universiti Teknologi MARA Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
² Atta-ur-Rahman Institute for Natural Products Discovery, Level 9, FF3, Universiti Teknologi MARA Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia. Electronic address: norhadiani@salam.uitm.edu.my.
³ Department of Chemistry, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
⁴ Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia; Faculty of Health and Medical Sciences, School of Biosciences, Taylor's University Lakeside Campus, 47500, Subang Jaya, Malaysia.
⁵ Chemistry Department, College of Sciences and Humanities, Prince Sattam Bin Abdulaziz University, P.O. Box 83, 11942, Al Kharj, Saudi Arabia.
⁶ Natural Products Research Group, Department of Chemistry, University of Surrey, Guildford, GU2 7XH, Surrey, United Kingdom; School of Chemistry and Physics, University of Natal, Durban, 4041, South Africa.

PMID: 30316148
DOI: 10.1016/j.phytochem.2018.10.002

Abstract

A phytochemical investigation of the stem barks of the Malaysian Croton oblongus Burm.f. (Syn. Croton laevifolius Blume) (Euphorbiaceae) yielded seven previously undescribed ent-neo-clerodane diterpenoids, laevifins A - G and the known crovatin (3). Structures were established by a combination of spectroscopic methods including HRESIMS, NMR spectroscopy and X-ray crystallography. The absolute configuration of crovatin and laevifins A-G was established by comparison of experimental ECD and theoretical TDDFT ECD calculated spectra. This is the first report on the occurrence of the sesquiterpenoid cryptomeridiol in a Croton species. In vitro cytotoxicity assays on laevifins A, B and G showed moderate activities against the MCF-7 cancer cell line (IC₅₀ 102, 115 and 106 μM, respectively) while β-amyrin and acetyl aleuritolic acid showed good anti-inflammatory activity on the LPS-induced NF-κB translocation inhibition in RAW 264.7 cells assay with IC₅₀ values of 23.5 and 35.4 μg/mL, respectively.

Keywords: Croton oblongus; Cytotoxicity; Euphorbiaceae; Laevifins A – G.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Proliferation / drug effects
Croton / chemistry*
Diterpenes, Clerodane / chemistry
Diterpenes, Clerodane / isolation & purification
Diterpenes, Clerodane / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
MCF-7 Cells
Mice
Molecular Conformation
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
Plant Bark / chemistry*
Plant Extracts / chemistry
Plant Extracts / isolation & purification
Plant Extracts / pharmacology*
Quantum Theory
RAW 264.7 Cells
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents, Phytogenic
Diterpenes, Clerodane
Lipopolysaccharides
NF-kappa B
Plant Extracts