Magie Melanie Kapojos
@prisma.ac.id
Pharmacy/Faculty of Science and Technology
Prisma University
RESEARCH INTERESTS
Natural Product Chemistry, Pharmacology, Chemistry, Toxicology and Pharmaceutical, Medicine
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Satoshi Ohte, Hiroyuki Yamazaki, Ohgi Takahashi, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Delfly B. Abdjul, Wilmar Maarisit, Magie M. Kapojos, Huiping Zhang,et al.
Elsevier BV
A new unique sesquiterpene lactone, bicyclolamellolactone A (1), was isolated together with two known monocyclofarnesol-type sesquiterpenes, lamellolactones A (2) and B (3), from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea). The planar structure of 1 was assigned based on its spectroscopic data (1D and 2D NMR, HRESIMS, UV, and IR spectra). The relative and absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism spectra in combination with NOESY correlations. Compounds 1-3 inhibited bone morphogenic protein (BMP)-induced alkaline phosphatase activity in mutant BMP receptor-carrying C2C12 cells with IC50 values of 51, 4.6, and 20 μM, respectively.
Hiroyuki Yamazaki, Satoshi Ohte, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Delfly B. Abdjul, Wilmar Maarisit, Magie M. Kapojos, Michio Namikoshi, Takenobu Katagiri,et al.
MDPI AG
Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder with heterotopic ossification (HO) in soft tissues. The abnormal activation of bone morphogenetic protein (BMP) signaling by a mutant activin receptor-like kinase-2 (ALK2) leads to the development of HO in FOP patients, and, thus, BMP signaling inhibitors are promising therapeutic applications for FOP. In the present study, we screened extracts of 188 Indonesian marine invertebrates for small molecular inhibitors of BMP-induced alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation in a C2C12 cell line stably expressing ALK2(R206H) (C2C12(R206H) cells), and identified five marine sponges with potent ALP inhibitory activities. The activity-guided purification of an EtOH extract of marine sponge Dysidea sp. (No. 256) resulted in the isolation of dysidenin (1), herbasterol (2), and stellettasterol (3) as active components. Compounds 1–3 inhibited ALP activity in C2C12(R206H) cells with IC50 values of 2.3, 4.3, and 4.2 µM, respectively, without any cytotoxicity, even at 18.4–21.4 µM. The direct effects of BMP signaling examined using the Id1WT4F-luciferase reporter assay showed that compounds 1–3 did not decrease the reporter activity, suggesting that they inhibit the downstream of the Smad transcriptional step in BMP signaling.
Magie Melanie Kapojos, Delfly Booby Abdjul, Hiroyuki Yamazaki, Akiho Yagi, and Ryuji Uchida
Pharmaceutical Society of Japan
Bioassay screening using Indonesian plants, such as traditional foods (vegetables, spices, and tea) and folk medicinal herbs, identified eight protein tyrosine phosphatase (PTP) 1B inhibitory and two antibacterial plants. The leaves of Syzygium polyanthum (Wight) Walp. were examined in more detail to define PTP1B inhibitory components, resulting in the isolation of a new active acylbenzene (1) along with four related congeners of 1 (2-5) and four oleanane triterpenes (6-9). The structure of 1 was elucidated as 12-oxo-12-(2,3,5-trihydroxy-4-methylphenyl)dodecanoic acid based on its spectroscopic data. The acylbenzenes 1 and 3-5 inhibited PTP1B activity with IC50 values ranging between 9.5 and 14 µM, whereas the triterpenes 7-9 also suppressed this activity with IC50 values of 3.3-5.7 µM.
Magie M. Kapojos, Delfly B. Abdjul, Hiroyuki Yamazaki, Taichi Ohshiro, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Hiroshi Tomoda, Michio Namikoshi, and Ryuji Uchida
Elsevier BV
Callyspongiamides A (1) and B (2), two new sterol O-acyltransferase (SOAT) inhibitors, were isolated from the Indonesian marine sponge Callyspongia sp. together with a known congener, dysamide A (3). The structures of 1 and 2 were elucidated to be polychlorine-containing modified dipeptides based on their spectroscopic data. Compounds 1-3 inhibited both of the SOAT isozymes, SOAT1 and SOAT2, in cell-based and enzyme-based assays.
Delfly B. Abdjul, Hiroyuki Yamazaki, Wilmar Maarisit, Ryota Kirikoshi, Ohgi Takahashi, Fitje Losung, Magie M. Kapojos, and Michio Namikoshi
Elsevier BV
Abstract Research on protein tyrosine phosphatase (PTP) 1B inhibitors from terrestrial and marine natural resources identified N-isobutyl-2E-decenamide (1) and 3,4,5-tri-O-caffeoylquinic acid (2) as PTP1B inhibitory substances together with a new N-alkylamide (3) and two known congeners (4 and 5) from the aerial parts of Indonesian Spilanthes paniculata. The structure of 3 was elucidated as (2E, 7Z)-6,9-endoperoxy-N-2-methylbutyl-2,7-decadienamide based on its spectroscopic data. Compound 3 is a rare N-alkylamide derivative with an endoperoxide bridge, and only three natural products have been reported in this class. Compound 1 inhibited PTP1B activity with an IC50 value of 24 μM, whereas compound 2 exerted an inhibitory effect of 35% at 15 μM. This is the first study to report the inhibitory effects of an N-alkylamide derivative (1) on PTP1B activity.
Magie M. Kapojos, Delfly B. Abdjul, Hiroyuki Yamazaki, Ryota Kirikoshi, Ohgi Takahashi, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Kazuyo Ukai, and Michio Namikoshi
Elsevier BV
Abstract Three known polybromobiphenyl ether derivatives, 2-(2′,4′-dibromophenoxy)-3,5-dibromophenol (1), 2-(2′,4′-dibromophenoxy)-4,6-dibromophenol (2), and 2-(2′-dibromophenoxy)-3,4,5,6-tetrabromophenol (3), were identified as PTP1B inhibitors from the Indonesian marine sponge Lamellodysidea sp. (cf. L. herbacea) together with two new monocyclofarnesol-derived sesquiterpenes, lamellolactones A (4) and B (5). The structures of 4 and 5 were elucidated based on their spectroscopic data and comparisons with those for related compounds. Compounds 1–3 inhibited PTP1B activity with IC50 values of 5.3, 7.8, and 5.3 μM, respectively, while compounds 4 and 5 were not active at 38–40 μM. The selective activities of 1–3 against PTP1B over the other PTPs (T-cell PTP, CD45 tyrosine phosphatase, and vaccinia H-1-related phosphatase) showed that the position and/or number of Br atoms affected their inhibitory activities.
Delfly Booby Abdjul, Hiroyuki Yamazaki, Syu-ichi Kanno, Ryota Kirikoshi, Ayako Tomizawa, Ohgi Takahashi, Wilmar Maarisit, Fitje Losung, Henki Rotinsulu, Defny Silvia Wewengkang,et al.
Pharmaceutical Society of Japan
Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.
Delfly B. Abdjul, Hiroyuki Yamazaki, Wilmar Maarisit, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Magie M. Kapojos, Fitje Losung, Kazuyo Ukai, and Michio Namikoshi
Elsevier BV
During the search for new protein tyrosine phosphatase (PTP) 1B inhibitors, EtOH extracts from the aerial parts of Lantana camara L. (lantana) collected at Manado (Indonesia) and two subtropical islands in Japan (Ishigaki and Iriomote Islands, Okinawa) exhibited potent inhibitory activities against PTP1B in an enzyme assay. Four previously undescribed oleanane triterpenes were isolated together with known triterpenes and flavones from the Indonesian lantana. The EtOH extracts of lantana collected in Ishigaki and Iriomote Islands exhibited different phytochemical profiles from each other and the Indonesian lantana. Triterpenes with a 24-OH group were isolated from the Indonesian lantana only. Five known triterpene compounds were detected in the Ishigaki lantana, and two oleanane triterpenes with an ether linkage between 3β and 25 were the main components together with five known triterpenes as minor components in the Iriomote lantana. The structures of previously undescribed compounds were assigned on the basis of their spectroscopic data. Among the compounds obtained in this study, oleanolic acid exhibited the most potent activity against PTP1B, and is used as a positive control in studies on PTP1B.
Delfly B. Abdjul, Hiroyuki Yamazaki, Syu-ichi Kanno, Ayako Tomizawa, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Kazuyo Ukai, Magie M. Kapojos, and Michio Namikoshi
Springer Science and Business Media LLC
In the course of our studies on anti-mycobacterial substances from marine organisms, the known dimeric sphingolipid, leucettamol A (1), was isolated as an active component, together with the new bromopyrrole alkaloid, 5-bromophakelline (2), and twelve known congeners from the Indonesian marine sponge Agelas sp. The structure of 2 was elucidated based on its spectroscopic data. Compound 1 and its bis TFA salt showed inhibition zones of 12 and 7 mm against Mycobacterium smegmatis at 50 μg/disk, respectively, while the N,N’-diacetyl derivative (1a) was not active at 50 μg/disk. Therefore, free amino groups are important for anti-mycobacterial activity. This is the first study to show the anti-mycobacterial activity of a bisfunctionalized sphingolipid. Compound 13 exhibited weak PTP1B inhibitory activity (29% inhibition at 35 μM).
Wilmar Maarisit, Hiroyuki Yamazaki, Syu-ichi Kanno, Ayako Tomizawa, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Kazuyo Ukai, Magie M. Kapojos, and Michio Namikoshi
Elsevier BV
During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitors from marine organisms, the known tetramic acid derivative, melophlin C (1), was isolated as an active component together with the new nortriterpenoid saponin, sarasinoside S (2), and three homologues: sarasinosides A1 (3), I1 (4), and J (5), from the Indonesian marine sponge Petrosia sp. The structure of 2 was elucidated on the basis of its spectroscopic data. Compound 1 inhibited PTP1B activity with an IC50 value of 14.6μM, while compounds 2-5 were not active at 15.2-16.0μM. This is the first study to report the inhibitory effects of a tetramic acid derivative on PTP1B activity.
Wilmar Maarisit, Delfly B. Abdjul, Hiroyuki Yamazaki, Hajime Kato, Henki Rotinsulu, Defny S. Wewengkang, Deiske A. Sumilat, Magie M. Kapojos, Kazuyo Ukai, and Michio Namikoshi
Elsevier BV
Three new dimeric 3-alkyl pyridinium alkaloids, named haliclocyclamines A-C (1-3), were isolated together with five known congeners, cyclostellettamines A (4), B (5), C (6), E (7), and F (8), from the Indonesian marine sponge Haliclona sp. The structures of 1-3 were assigned based on their spectroscopic data (1D and 2D NMR, HRFABMS, ESIMS/MS, UV, and IR). Compounds 1-8 exhibited antimicrobial activities against Mycobacterium smegmatis with inhibition zones of 17, 10, 13, 14, 8, 8, 12, and 12mm, respectively, at 10μg/disc. Compounds 3 and 8 also modestly inhibited the activity of vaccinia H-1-related phosphatase (VHR), a dual-specificity phosphatase, at 17-18μM.
Delfly B. Abdjul, Hiroyuki Yamazaki, Syu-ichi Kanno, Defny S. Wewengkang, Henki Rotinsulu, Deiske A. Sumilat, Kazuyo Ukai, Magie M. Kapojos, and Michio Namikoshi
Elsevier BV
Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two furanosesterterpenes and a C21 furanoterpene were obtained as new types of PTP1B inhibitors from two Indonesian marine sponges. (7E, 12E, 20Z, 18S)-Variabilin (1) and (12E, 20Z, 18S)-8-hydroxyvariabilin (2) from Ircinia sp. and furospongin-1 (3) from Spongia sp. inhibited PTP1B activity with IC50 values of 1.5, 7.1, and 9.9μM, respectively. The inhibitory activity of compound 1 against T-cell PTP (TCPTP) was approximately 2-fold that against PTP1B, whereas the vaccinia H-1-related phosphatase (VHR) inhibitory effects of 1 were 4-fold weaker than that of its PTP1B inhibitory activity. Compounds 1-3 at 50μM did not show cytotoxicity against two human cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1. Compound 1 did not enhance the phosphorylation level of Akt, a key downstream effector of the cascade, in Huh-7 cells.
Magie M. Kapojos, Jong-Soo Lee, Taiko Oda, Takahiro Nakazawa, Ohgi Takahashi, Kazuyo Ukai, Remy E.P. Mangindaan, Henki Rotinsulu, Defny S. Wewengkang, Sachiko Tsukamoto,et al.
Elsevier BV
Abstract Two unusual cembranoids, sarcofuranocembrenolides A (1) and B (2), were isolated from a soft coral Sarcophyton sp. together with five known cembranoids (3–7). Compound 1 had a unique carbon skeleton of 8,19-bisnorfuranocembrenolide. Compound 2 was a furanocembrenolide, but a C1 unit (C-20) was attached to C-10 instead of C-12 of the ordinary cembrenolides. These rearrangements are unique in the biosynthesis of cembranoid diterpenes. Lobohedleolide (5), (7Z)-lobohedleolide (6), and denticulatolide (7) inhibited the colony formation of V79 cells at ED50 values of 4.6 (abt. 1.52), 3.7 (1.22), and 3.6 (1.40) μM (μg/mL), respectively, and reduced TNF-α production from LPS-stimulated RAW264.7 cells at 3.0–10.0 μM.
Magie Melanie Kapojos, Remy Emile Petrus Mangindaan, Takahiro Nakazawa, Taiko Oda, Kazuyo Ukai, and Michio Namikoshi
Pharmaceutical Society of Japan
Three new sesquiterpenes, 2-deoxy-7-O-methyllemnacarnol (1), 2-deoxy-12 alpha-ethoxy-7-O-methyllemnacarnol (2), and 2-deoxy-12 alpha-methoxy-7-O-methyllemnacarnol (3), were isolated from a soft coral Nephthea sp. collected in Indonesia, together with five known sesquiterpenes. The structures of the new compounds were assigned on the basis of their spectroscopic data.