Metabolic Activation and Toxicities of Furanoterpenoids

Li, H.; Peng, Ying; Zheng, Jiang

doi:10.1016/b978-0-12-804700-2.00002-7

Cited by 9 publications

(7 citation statements)

References 213 publications

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“…However, the γ‐ketoenal has been trapped with range of species including semicarbazide which can form a pyridazine (Scheme 2). [15c] Therefore, we undertook in vitro CYP199A4‐catalyzed oxidations of 4‐(furan‐2‐yl)benzoic acid in the presence of semicarbazide. GC‐MS analysis of the reactions after derivatization identified a new metabolite with a mass of 272.2 which is in agreement with the expected mass of the TMS‐derivatized 4‐(pyridazin‐3‐yl)benzoic acid (272.1; Scheme 2 and Figure S12).…”

Section: Resultsmentioning

confidence: 99%

The Oxidation of Oxygen and Sulfur‐Containing Heterocycles by Cytochrome P450 Enzymes

Podgorski

Keto

Coleman

et al. 2023

Chemistry A European J

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The cytochrome P450 (CYP) superfamily of monooxygenase enzymes play important roles in the metabolism of molecules which contain heterocyclic, aromatic functional groups. Here we study how oxygen‐ and sulfur‐containing heterocyclic groups interact with and are oxidized using the bacterial enzyme CYP199A4. This enzyme oxidized both 4‐(thiophen‐2‐yl)benzoic acid and 4‐(thiophen‐3‐yl)benzoic acid almost exclusively via sulfoxidation. The thiophene oxides produced were activated towards Diels‐Alder dimerization after sulfoxidation, forming dimeric metabolites. Despite X‐ray crystal structures demonstrating that the aromatic carbon atoms of the thiophene ring were located closer to the heme than the sulfur, sulfoxidation was still favoured with 4‐(thiophen‐3‐yl)benzoic acid. These results highlight a preference of this cytochrome P450 enzyme for sulfoxidation over aromatic hydroxylation. Calculations predict a strong preference for homodimerization of the enantiomers of the thiophene oxides and the formation of a single major product, in broad agreement with the experimental data. 4‐(Furan‐2‐yl)benzoic acid was oxidized to 4‐(4′‐hydroxybutanoyl)benzoic acid using a whole‐cell system. This reaction proceeded via a γ‐keto‐α,β‐unsaturated aldehyde species which could be trapped in vitro using semicarbazide to generate a pyridazine species. The combination of the enzyme structures, the biochemical data and theoretical calculations provides detailed insight into the formation of the metabolites formed from these heterocyclic compounds.

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Section: Resultsmentioning

confidence: 99%

The Oxidation of Oxygen and Sulfur‐Containing Heterocycles by Cytochrome P450 Enzymes

Podgorski

Keto

Coleman

et al. 2023

Chemistry A European J

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“…Author details 1 Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia. 2 Central Laboratory, Universitas Padjadjaran, Jatinangor 45363, Indonesia. 3 Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60286, Indonesia.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…Limonoids, known as degraded triterpenes, are derived from a precursor with a 4,4,8-trimethyl-17-furanylsteroid four-ring skeleton labelled as A, B, C and D rings [1]. Limonoids are a class of secondary metabolites found in the order Rutales and the Meliaceae and Rutaceae family [2]. Meliaceae is a family of timber trees that are a rich source for limonoids and are widely distributed in tropical and subtropical regions with 50 genera and more than 1400 species [3,4].…”

Section: Introductionmentioning

confidence: 99%

A new havanensin-type limonoid from Chisocheton macrophyllus

et al. 2021

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A new havanensin-type limonoid, 16β-hydroxydysobinin (1), along with four known limonoids (2–5), have been isolated from the seeds of Chisocheton macrophyllus. The chemical structure of the new compound was determined by referencing spectroscopic data, and by comparison to those related spectra previously reported. Each compound was evaluated for their cytotoxic effects against Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and display no significant activity.

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“…Biosintesis limonoid secara garis besar meliputi tiga langkah, yaitu (1) epokdasi prekursor, menghasilkan ion tetrasiklik; (2) degradasi oksidatif pada C-17 yang menyebabkan hilangnya empat atom karbon dan pembentukan cincin furan tersubstitusi-β; (3) oksidasi lebih lanjut dan penataan ulang kerangka menghasilkan senyawa-senyawa limonoid yang memiliki struktur dan aktivitas biologis berbeda-beda (Li et al, 2016). Sampai saat ini, sekitar 1300 limonoid dengan lebih dari 35 kerangka struktural yang beragam telah dilaporkan.…”

Section: Senyawa Limonoid Dari Tumbuhan Chisochetonunclassified

Senyawa Golongan Limonoid dari Tanaman Genus Chisocheton dan Aktivitas Antikankernya

2021

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Indonesia merupakan negara yang kaya akan keanekaragaman hayati. Terdapat banyak tanaman yang mengandung senyawa metabolit sekunder yang memiliki aktivitas biologi sehingga berpotensi untuk digunakan sebagai obat, salah satunya adalah genus Chisocheton. Tanaman genus Chisocheton sudah banyak dilaporkan mengandung senyawa triterpenoid, seskuiterpenoid, limonoid, steroid, dan fenol. Limonoid merupakan turunan triterpenoid yang paling banyak ditemukan pada tanaman genus Chisocheton. Lebih dari tiga puluh senyawa golongan limonoid telah diuji aktivitas antikankernya terhadap beberapa jenis sel kanker manusia, seperti sel kanker payudara, mulut, paru-paru, leukimia, serviks, dan hati. Beberapa senyawa limonid tersebut diketahui memiliki aktivitas sitotoksik yang tinggi dengan kisaran nilai IC50 1,67 − 50,27 µg/mL. Review ini memaparkan beberapa senyawa limonoid yang diisolasi dari genus Chisocheton, aktivitas sitotoksiknya terhadap sel-sel kanker manusia, serta hubungan struktur dan aktifitas biologisnya (SAR = Structure Activity Relationship). Selain itu beberapa penelitian juga sudah melakukan penelitian lebih lanjut seperti pengujian induksi apoptosis dan penentuan tingkat ekspresi gen-gen yang berhubungan dengan apoptosis. Penelitian-penelitian yang dilakukan ini mengarah pada pencarian senyawa baru yang dapat digunakan sebagai lead compound untuk mendapatkan obat antikanker yang efektif.Limonoid Compounds from Genus Chisocheton Plant and Its Anticancer Activity. Indonesia is a country with a large biodiversity. There are many plants contain secondary metabolite compounds with biological activity, such as Chisocheton genus. The Chisocheton is reported as plant with triterpenoids, sesquiterpenoids, limonoids, steroids and phenols content. Limonoids arethe derivative of triterpenoid which mostly found in Chisocheton genus. More than thirty limonoids have been studied for their anticancer activity against several types of human cancer cells, such as breast, mouth, lung, leukemia, cervical, and liver cancer cells. Some of these limonoids are known to have high cytotoxic activity with the IC50 values of 1.67 − 50.27 µg/mL. This review discuss many kind of limonoid compounds isolated from Chisocheton, their cytotoxic activity against human cancer cells, and their structural activity relationship (SAR) study. This review also discusses some research result for further studies of Chisocheton wether in the mechanism of apoptosis induction and also the determination genes level expression or proteins associated with the apoptosis. This review reveals the important of the study to find a new compounds for an effective anticancer drug.

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Metabolic Activation and Toxicities of Furanoterpenoids

Cited by 9 publications

References 213 publications

The Oxidation of Oxygen and Sulfur‐Containing Heterocycles by Cytochrome P450 Enzymes

The Oxidation of Oxygen and Sulfur‐Containing Heterocycles by Cytochrome P450 Enzymes

A new havanensin-type limonoid from Chisocheton macrophyllus

Senyawa Golongan Limonoid dari Tanaman Genus Chisocheton dan Aktivitas Antikankernya

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