PHYTOCHEMICAL STUDY AND CYTOTOXIC ACTIVITY OF SECONDARY METABOLITE FROM SOME INDONESIAN CRYPTOCARYA (LAURACEAE)

• Main Author: Suwandri
• Format: Dissertations
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/34274
• Institution: Institut Teknologi Bandung

Cryptocarya belongs to the plant family Lauraceae spreading widely in the tropical and subtropical regions of Asia, Australia and Melanesia. In Indonesia, Cryptocarya is well known as "medang" or "huru". The people of this region uses the plants for building and furnishing materials, and as raw materials of pulps for paper industry, which makes them have important economic values. In addition, a number of the plants have also been used in the folk medicines for skin diseases, muscle and joint pains, headaches, nausea, infections due to fungi and bacteria. These uses have motivated phytochemical studies conducted on this genus. Phytochemical studies have shown that Cryptocarya plants produce various types of secondary metabolites, including alkaloids, 2-pyrones, flavonoids, lignans, terpenoids and steroids. The diversity of these secondary metabolites has made this genus is not homogeneous. The alkaloids and 2–pyrones, and flavonoids are more prominent character of Cryptocarya. Alkaloids, in particularly, are characteristic to the Australian Cryptocarya, while 2-pyrones and flavonoids have been also reported to occur in other species. Biogenetically, 2-pyrones and flavonoids can be regarded to be formed from the same common pathways, namely C6-C3-oligoketides (n C2), in which the flavonoid is a particular pathway of C6-C3-three-ketides (C6). However, some of the plants, such as C. massoy, produced 2-pyrones of a pure ketide pathway (n C2). From previous results, Indonesian Cryptocarya producing alkaloids seemed to have no geographical characteristics and were relatively produced limited in amount. Besides, the presence of alkaloids on one hand, and 2-pyrones and flavonoids on the other hand does not occur in the same species. In other words, the species that produce alkaloids as the primary metabolites most lilkely are not accompanied by the presence of 2-pyrones and flavonoids, and if it is synthesized, these metabolites are produced in the very small amounts, and vice versa. Based on these backgrounds, this research has been conducted to carry out phytochemical studies on four species of Indonesian Cryptocarya, namely C. archboldiana C. crassinerviopsis, C. palawanensis, and C. subvelutina. The research also examined the cytotoxic properties of the isolated compounds against murine leukemia cells P-388 as well as revealing the structure relationship of the compounds with the bioactivities. The materials used in this research were the bark part of the plants collected from various regions of Indonesia. The barks of C. crassinerviopsis and C. subvelutina were collected from Kendari, Southeast Sulawesi, while the barks of C. archboldiana and C. palawanensis were collected from Merauke, Papua, and Halmahera, North Maluku, respectively. The isolation of the secondary metabolites were carried out involving several laboratory works, including extraction, fractionation and purification, using various chromatographic techniques. The molecular structure of the isolated compounds were determined by analysis of spectroscopic data, including UV, 1D NMR, 2D NMR and mass spectroscopy. The cytotoxic effect of the isolated compounds was evaluated against murine leukemia cell P-388 using MTT method [3-(4,5-dimethylthiazo-2- yl)-2,5-diphenyltetrazolium bromide]. The phytochemical investigation has successfully isolated ten pure compounds, including a new compound, namely cryptocrassinerviopsilic acid (1). The remaining of the isolated compounds are known compounds, including two flavanones, i.e pinocembrine (2) and pinostrobin (3); two chalcone derivatives, namely cryptocaryone (4) and kurzichalcolactone A (5), an alkaloid benzyltetrahydroisoquinoline, reticuline (8), as well as four aporphine alkaloids, namely laurolitsine (6), boldine (7), nandigerine (9) and N-methylnandigerine (10). The isolation of the new compound cryptocrassinerviopsilic acid (1) is an important of chemical data of Cryptocarya plants. It has a unique structure with a tetracyclic [5.3.14,10.06,8]undek-2-en skeleton and was elucidated unambigously based on spectroscopic data including 1H NMR, 13C NMR, ADEQUATE, TOCSY1D, HSQC, HMBC, and NOESY. Based on the cytotoxic activity evaluation of the isolated compounds, only cryptocaryone (4) that showed a strong cytotoxic activity against murine leukemia cells P-388, while the nine other compounds have low cytotoxic properties, and even inactive. Structural relationships to the cytotoxicity indicated that the chalcone derivative containing a tetrahydrobenzofuranone unit (lactone ring) and a reduced ring A in the structure of cryptocaryone (4) could be an important pharmacophore of strong cytotoxic effect. In conclusion, this research has shown that Cryptocarya does not only produce alkaloids, flavonoids, and 2-pyrons, but also a long-chain polyenes carboxylic acid derivatives (i.e cryptocrassinerviopsilic acid (1)), which can be regarded as an extension of the the capability of the polyketide pathway, and it has an important implication to its relationship to the genera Persea and Litsea. The presence of simple flavanone derivatives, pinocembrine (2) and/or pinostrobin (3), together with cryptocrassinerviopsilic acid (1), and cryptocaryone (4) with kurzichalcolactone A (5), without the presence of alkaloids, reflects a change of the alkaloid formation to the polyketide pathway occuring in the Indonesian Cryptocarya. The alkaloids found in C. archboldiana and C. subvelutina, which are originated from the Eastern part of Indonesia, shows a close relation of these plants with the Australian Cryptocarya.