STUDI FITOKIMIA DAN SITOTOKSISITAS SENYAWA FENOL DARI DAUN BEBERAPA SPESIES ARTOCARPUS

• Main Author: Eliza
• Format: Dissertations
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/81128
• Institution: Institut Teknologi Bandung

Artocarpus, locally known as nangka-nangka-an, is one of the important genera of Moraceae family. This genus is very popular in Indonesia because some of them produces delicious and nutritious fruits such as “nangka” (A. heterophyllus), “cempedak” (A. champedens), “sukun” (A. communis), and “keluih” (A .altilis). Their woods are used for building construction, and these plants are also widely used in folk medicines, such as to treat malarial fever, dysentery, tuberculosis, ulcer, diabetes and anti-inflammatory. At least, thirteen Indonesia Artocarpus have been investigated. Phytochemical study on Artocarpus species showed that these plants are rich sources of prenylated phenolic, particularly flavonoids. The prenylated flavonoids distribute not only on the roots or stems but also on the leaves. Some of them also exhibite a variety of interesting biological activities, such as cytotoxic against some human cell lines cancers and tumors, anti-platelet, anti-inflammatory, anti-malarial, antiviral and antimicrobial tuberculosis. A plenty of phenolic compounds, i.e. prenylated flavonoids, have been obtained from the roots and stems, however the report on the phenolic compounds from the leaves are still limited. The leaves of three species of Artocarpus have been investigated previously and it was reported that there are chemical differences in pattern of their phenolic compounds between leaves and roots or stems. The first difference is the type of flavonoids. The flavonoids obtained from leaves of Artocarpus are chalcones, dihydrochalcones and flavanones while their roots or stems yield mainly yielded flavones types. The second difference is the oxygenation pattern in the B-ring of flavonoid. The flavonoids from Artocarpus leaves possess monooxygenation or orto dioxygenation at B-ring, while the flavonoids from roots and stems generally have C2’, C4’-dioxygenation or C2’, C4’, C5’-trioxygenation pattern. The other difference is the attachment position of prenyl substituent at flavonoid skeleton. Some of flavonoid from leaves have prenyl group substituted at B ring which is very rarely found in roots or stems. Based on the background, the objectives of this research are to study the chemistry profile of phenolic compounds from the leaves of four species of Artocarpus, namely A. communis, A. altilis, A. kemando, and A. lanceifolius and also to evaluate cytotoxicities of the isolated compounds against murine leukemia P-388 cells. Regarding to the variety of chemical structures and their IC50 values therefore the structure-activity relationship of these compounds are also analyzed. The samples of leaves of A. communis and A. altilis were collected from South Sumatra, A. kemando was from the botanical garden in Bogor, while A. lanceifolius was from West Sumatra. The isolation of the phenolic compounds involved a number of laboratory works, including extraction, fractionation and purification, using various chromatography techniques. The molecular structures of the isolated compounds were determined based on spectroscopic data, including UV, IR, 1DNMR (1H and 13C), 2D-NMR (HMQC, HMBC, and NOESY), and high resolution mass spectrometry. The cytotoxic activity of the isolated compounds was evaluated against murine leukemia P-388 cells using MTT [3-(4, 5-dimethyltiazo-2-yl) 2, 5- diphenyltetrazolium bromide] method. In this phytochemical investigation, three new dihydrochalcones identified as artoindonesianin C1 (1), artoindonesianin C2 (2) and artoindonesianin C3 (3) have been isolated from leaves of Artocarpus along with nine known phenolic compounds. The known compounds including two dihydrochalcones (AC-5-1 (4), and 4,4’-di-Omethylphloretine (5)), four flavanones (7,4’-di-O-methylnaringenin (7), 8-isoprenyl- 4’-O-methylnaringenin (8), 8-geranylnaringenin (8), and 3’-geranylnaringenin (9)), and two flavanonols (dihydroikaritin (10) and lespedezaflavanone C (11)) and a flavones (cyclocommunol (12)). The phenolic compounds isolated from Artocarpus leaves have different chemical pattern compared to the phenolic compounds derived from roots and stems. The differences are the type of flavonoids, the oxygenation pattern in the B-ring, and the position of prenyl group at the B-ring. The finding of three new compounds and the differences of chemical pattern of phenolic compound between the leaves and the roots or stems of Artocarpus prove the ability of Artocarpus plant to produce phenolic compounds with varying groups and structures. Generally, the formation of flavonoid compounds in Artocarpus leaves follows a common biosynthetic pathway take place in other plants. The presence of flavanones having prenyl group at C-8 position can suggest that biogenetically the prenylation at flavones skeleton occur after cyclization to form flavanones but not after chalcones formation. The phytochemical study carried out in Artocarpus species also contributes on chemotaxonomy field and it can support previous assumption on evolution level and phylogenetic between species in Artocarpus genus. The cytotoxicities study against murine leukemia P-388 cells showed that a phenolic compound, i.e. cyclocommunol (12), is very active with IC50 1.9 ?g/mL whereas three phenolic compounds, namely 3’-geranylnaringenin (9), lespedezaflavanon C (11) and AC 5-1 (4), are active with IC50 3.2, 3.4, and 3.6 ?g/mL, respectively. Based on these results, the structure-activity relationship of the isolated compounds and their cytotoxities against P-388 could be suggested. The presence of isoprenyl or geranyl group at phenolic skeleton tends to increase the cytotoxicity, and the cytotoxicity increase when the isoprenyl or geranyl substitutes at B ring. However, the modification at geranyl group will cause the decreasing of the cytotoxicity. In conclusion, three new compounds, namely artoindonesianin C1 (1), artoindonesianin C2 (2) and artoindonesianin C3 (3), have been successfully isolated in this research. The discovering of twelve phenolic compounds from leaves of Artocarpus, undoubtfully proves that there are some differences on chemical pattern of phenolic compounds between leaves and roots or stems. In addition, it also can show that Artocarpus has the ability to produce a variety of phenolic compounds. Furthermore, the results of the cytotoxic evaluation of isolated compounds against P- 388 cells show that there is relation between the presences of isoprenyl or geranyl substituents at phenolic skeleton to the cytotoxic activity.