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BAB V KESIMPULAN DAN SARAN 5.1 Kesimpulan 1. Senyawa alkaloid hasil isolasi daun Pule (Alstonia scholaris) adalah suatu alkaloid indol golongan kerangka aspidodasikarpin CO 2 CH
3
H H O
O
OCH
3
N N H
H
H
2. Senyawa alkaloid dari daun Alstonia scholaris memiliki aktivitas sebagai antiplasmodial dalam uji in vitro terhadap Plasmodium falciparum dengan nilai IC50 sebesar 1,926 μg/ml
5.2 Saran Disarankan agar dilakukan uji aktivitas antimalaria terhadap senyawa murni alkaloid indol golongan kerangka aspidodasikarpin untuk mengetahui aktivitas antimalarianya. Sehingga senyawa alkaloid ini dapat digunakan sebagai obat antimalaria.
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DAFTAR PUSTAKA
Abe, F., Chen, R., Yamauchi, T., Marubayashi, N., Ueda, I, 1989, Alscomine and Isoalschomine, New Alkaloids from the Leaves of Alstonia scholaris, Faculty of Pharmaceutical Sciences, Fakuoka University, Japan, Vol 37, 887-889. Abe, F,Yamauchi, H, S, Isao, K, and Masami, Y, 1998, Indole Alkaloids from the Leaves of Alstonia villosa in Sumbawa, Pharmaceutical Science, Fakuoka , Japan, Vol 46, 1235-1238 Benerji, A., Sidhanta, A.K. 1981. Scholarine: an indole alkaloid of Alstonia scholaris, Phytochemistry, 20, 540-542 . Benerji, J., Mustafi, R., Roy, D.J. 1984. (-)-Scholarine and (+)-Iochneridineconstituents of Alstonia scholaris R.Br. (Apocynaceae), Indian J. Chem, Section B: Organic Chemistry Including Medicinal Chemistry, 23(B), 455. Boonchuay, W., Court, W.E. 1976. Minor alkaloids of Alstonia scholaris Root, Phytochemistry, 15, 821-822. Buckingham, J. 1994. Dictionary of Natural Product, Chapman & Hall, London Cai, X., Du, Z., Luo, X., 2007, Unique Monoterpenoid Indole Alkaloids from Alstonia scholaris, State Key Laboratory of Phytichemistry and Plant Resources in West China, Vol 9, 1817-1820. Carroll, Anthony R., Edward H, Jill S, Ronald J. Q, Gordon G, and Paul I. F, 2004, Actinophyllic Acid, a Potent Indole Alkaloid Inhibitor of the Coupled Enzyme Assay Carboxypeptidase U/Hippuricase from the Leaves of Alstonia actinophylla, Natural Product Discovery, Brisbane Botanic Gardens, Toowong, Australia. Cordell and Geoffrey A., 2006, Introduction to Alkaloid, John Willey and Sons, Toronto. Dyatmiko, Wahjo, 60 Persen Ada Di Tumbuhan Obat, http://www.antara.co.id, 30 November 2010. Doolan and Denise L. Malaria Methods and Protocols. Humana Press,inc, Totowa, Vol 72
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Elisabetsky, E., Campos, L. Costa., 2006. The Alkaloid Alstonine : A review of Its Pharmacological Properties, Laboratorio de Etnofarmacologia, ICBS, Universade do Rio Grande do Sul, Brazil. Feng, T., Li, Y., chun, X, H., Gong, X., Liu,Y, Ting, Rong, Z., Qin, T G,. Luo, X D., 2009, Monoterpenoid Indole Alkaloids from Alstonia yunnanensis, State Key Laboratory of Phytochemistry and Plant Resources In West China, Vol 72, 1836-1841. Fidock,A., David, 2004, Antimalarial Drugs Discovery Model for Compound Screening, Departement of Microbiology and Immunology, Albert Einst College of Medicine, 1300 morris park avenue, Bron New York, USA Frederich, Michael., Tits, Monique., Anenot, Luc., 2007, Potensial Antimalaria Activity Of Indole Alkaloid, Journal of Pharmaci Research, Vol 102, 11-19. Ghedira, K., Hanrot, M.Z., Richard, B., Massiot, G., Olivier, L., Sevenet, T., Goh, S.H, 1988, Alkaloid of Alstonia Angustifolia, Faculte de Parmecie, University of Malaya, Malaysia, Vol 27, 3955-3962. Harbone, J.B., 1987, Metode Fitokimia, diterjemahkan Padmawinata, ITB, Bandung. Harijanto1, P.N., Nugroho, A., Gunawan.,Carta A., 2006, Malaria dari Molekuler ke Klinis, Edisi 1. Buku Kedokteran EGC, Jakarta, Indonesia. Harijanto2, P.N., Nugroho, A., Gunawan.,Carta A., 2010, Malaria dari Molekuler ke Klinis, Edisi 2. Buku Kedokteran EGC, Jakarta, Indonesia. Heyne,K. 1987. Tumbuhan Berguna Indonesia, terjemahan Badan Litbang Kehutanan, Jilid III, Cetakan kesatu, Badan Penelitian dan Pengembangan Kehutanan, Departemen Kesehatan. Hirasawa, Y., Arai, H., Zaima, K., Oktarina, R , Rahman, A., Ekasari, Wiwied., w, Aty., Indrayanto, Gunawan, Zaini , Noor C and H, Morita., 2008, Alstiphyllanines A-D, Indole Alkaloids from Alstonia macrophylla, Faculty of Pharmaceutical Science, Tokyo, 72 (2): 304-307. Kam,
T and Choo, Y, 2004, Alkaloid from Alstonia angustifolia, Phytochemistry,department of Chemistry, University of Malaya, Malaysia Depart 65(5): 603-608.
Kohler, I and Siems, K., 2002, In vitro Antiplasmodial Investigation of Medicinal Plants from Elsavador.Z., Naturforsch, 57c, 277-278
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Koyama, Koichiro., Hirasawa., Yusuke., , Eko,N A., Hosoya, T., Hoe, Chin., C, KitLam, and, Morita, H. , 2010, Alsmaphorazines A and B, Novel Indole Alkaloids from Alstonia pneumatophora, Faculty of Pharmaceutical Science, Malaysia. Liu, X., Deschamp, Jeffry R., and M.Cook, James., 2002, Regiospesicific, Enantiospesicifik Total Synthesis Of The Alkoxy-Subtituted Indole Bases, 16epi-Na-Methylgardneral, 11-Methoxyaffinisine, and 11-Methoxymacroline as Well as the Indole Alkaloids Alstophylline and Macralstonine, Journal Naval Research Laboratory, vol 4, 3339-3342. Morita, Y., Hesse, M., Schmid, H., Banerji, J., Chatterji, A., Oberhaensli, W.E. 1977. Alstonia scholaris: structure of the indole alkaloid nareline, Helv, Chim, Acta., 60(4), 1419-1434. Nuri, 2006. Aktivitas Antimalaria Isolat yang Berasal dari Ekstrak Diklorometana Kulit Batang Artocarpus Champeden Spreng Secara In vitro, Tesis, Universitas Airlangga, Surabaya. Oullette. Robert, J. 1998. Organic Chemistry A Brief Introduction, second edition, Prentice Hall, New Jersey. Patrick, A., G, Macabeo., K, Karsten, G, Dietmar,. W.Read, Roger., B, Joseph, Cordel, J.,Geoffrey A., Franzblau, S, G., M. Aguinaldo, A , 2005. Indole Alkaloids from Leaves of Philipine Alstonia scholaris. Phytochemistry Laboratory, Research Center for the Natural Science, Philipines, Vol 66, 1158-1162. Pusarawati, S., Tantular, I., 2005, Diagnostik Mikroskopis Malaria Pewarnaan Giemsa dan Akridil Orange (AO). Bag. Parasitologi Fakultas Kedokteran dan Tropical Disease Center(TDC), Universitas Airlangga, Surabaya. Rahman, Atta-UR., and, Basha, A., 1983, Biosynthesis of Indole Alkaloids, Oxford University Press, London. Renia, L, Miltgen, F., Charoenvit, Y., Ponnudurai, T., Verhave, J.P., Collins, W.E, and Mazier, D. 1988, Malaria sporozoite penetration: a new approach by double staining. J. Immunol. Methods 112, 201-205. Salim AA, Garson MJ, Craik, DJ., 2004, New Indole Alkaloids from the bark of Alstonia scholaris, Institute for Molecular Bioscience and Departement of Chemistry, University of Quensland, Brisbane, 67(9): 1591-4.
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Schlesinger, P.H., Krogstad, D.J., Herwaldi, B.L., 1988, Antimalarial agent: mechanism of action., June, 793-798. Strickland,G.T., and Hoffman, 1994. Strategies for the Control of Malaria, Science and Medicine, 1, 1, 24-33. Tan, Shin J., low, Yun, Y., Choo, Y, Mun., Abdullah, Z, , Etoh, Tadahiro,., Hayashi, M., Kanki, K., kam, T S., 2010. Strychnan and Secoangustilobine A Type Alkaloids from Alstonia spatulata C-20 Configuration of Scholaricine, Departemen of Chemistry, University of Malaya, Malaysia, Vol 73, 18911897. WHO, 2009, World Malaria Report. Regional office for South East Asia, 30 November 2010. Yamauchi, T., Fumiko, A., William G., Padolina, and Fabian, M., Dyart., 1990. Alkaloids From The Leaves Of Alstonia Sholaris In Taiwan, Thailand, Indonesia And The Philippines. Faculty of Pharmaceutical Sciences, Fakuoka University, Fakuoka, Japan. Yinusa, R., Toyin, M. Salman O,S, Akinsomisoye, 2005, Reproductive Functions In Male Rats Treated With Methanolic Extract of Alstonia Boonei Steam Bark, African Journal of Biomedical Research, Vol.8(2): 105-111.
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Lampiran 1 Spektrum senyawa B Spektrum 13C-NMR
Spektrum 1H-NMR
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Spektrum IR
Spektrum UV-Vis
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Lampiran 2 Hasil Uji Antiplasmodial Ekstrak Alkaloid daun Alstonia scholaris Konsentrasi uji (μg/ml) Kontrol (-) 100 10 1 0,1 0,01
Skripsi
R 1 2 1 2 1 2 1 2 1 2 1 2
% Parasitemia 0 jam 48 jam 1,2 3,80 1,3 2,90 1,2 0,70 1,3 1,10 1,2 1,80 1,3 1,66 1,2 2,40 1,3 2,00 1,2 2,60 1,3 2,20 1,2 3,20 1,3 2,50
% Pertumbuhan
% Hambatan
2,60 1,60 0 0 0,60 0,36 1,20 0,70 1,40 0,90 2,00 1,20
100 100 76,92 77,50 53,85 56,25 46,15 43,75 23,07 25,00
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% Hambatan rata-rata 100 77,21 55,05 44,95 24,04
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Probit Ekstrak Alkaloid daun Alstonia scholaris PROBIT Konsentrasi OF total WITH penghambatan /LOG 10 /MODEL PROBIT /PRINT FREQ CI /CRITERIA P(0.15) ITERATE(20) STEPLIMIT(.1).
Data Information N of Cases Valid Rejected Missing LOG Transform Cannot be Done Number of Responses > Number of Subjects Control Group
5 0 0 0 0
Convergence Information Number of Iterations
Optimal Solution Found
PROBIT 20 Noa a. Parameter estimates did not converge.
Parameter Estimates 95% Confidence Interval Parameter PROBITa penghambatan
Estimate Std. Error 24.313
2.343
Z 10.375
Sig. .000
Lower Bound Upper Bound 19.720
28.906
Intercept -46.824 4.487 -10.436 .000 -51.311 -42.337 a. PROBIT model: PROBIT(p) = Intercept + BX (Covariates X are transformed using the base 10.000 logarithm.)
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Chi-Square Tests dfa
Chi-Square
Sig.
PROBIT Pearson Goodness-of4.381E33 3 .000b Fit Test a. Statistics based on individual cases differ from statistics based on aggregated cases. b. Since the significance level is less than .150, a heterogeneity factor is used in the calculation of confidence limits.
Cell Counts and Residuals Num Number of ber penghambatan Subjects PROBIT
Observed Responses
Expected Responses
Probabilit Residual y
1
2.000
100
100
96.425
3.575
.964
2
1.888
100
10
17.651
-7.651
.177
3
1.741
100
1
.000
1.000
.000
4
1.653
100
0
.000
.100
.000
5
1.381
100
0
.000
.010
.000
Confidence Limits
PR OBI Ta
Skripsi
95% Confidence Limits for penghambatan
95% Confidence Limits for log(penghambatan)b
Prob abilit y
Estimate
Lower Bound
Upper Bound
Estimate
Lower Bound
Upper Bound
.010
67.638
.
.
1.830
.
.
.020
69.407
.
.
1.841
.
.
.030
70.553
.
.
1.849
.
.
.040
71.428
.
.
1.854
.
.
.050
72.147
.
.
1.858
.
.
.060
72.765
.
.
1.862
.
.
.070
73.312
.
.
1.865
.
.
.080
73.804
.
.
1.868
.
.
.090
74.255
.
.
1.871
.
.
.100
74.673
.
.
1.873
.
.
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.150
76.427
.
.
1.883
.
.
.200
77.850
.
.
1.891
.
.
.250
79.092
.
.
1.898
.
.
.300
80.224
.
.
1.904
.
.
.350
81.288
.
.
1.910
.
.
.400
82.310
.
.
1.915
.
.
.450
83.311
.
.
1.921
.
.
.500
84.309
.
.
1.926
.
.
.550
85.318
.
.
1.931
.
.
.600
86.356
.
.
1.936
.
.
.650
87.442
.
.
1.942
.
.
.700
88.602
.
.
1.947
.
.
.750
89.870
.
.
1.954
.
.
.800
91.304
.
.
1.960
.
.
.850
93.004
.
.
1.969
.
.
.900
95.188
.
.
1.979
.
.
.910
95.723
.
.
1.981
.
.
.920
96.308
.
.
1.984
.
.
.930
96.955
.
.
1.987
.
.
.940
97.683
.
.
1.990
.
.
.950
98.520
.
.
1.994
.
.
.960
99.513
.
.
1.998
.
.
.970
100.747
.
.
2.003
.
.
.980
102.410
.
.
2.010
.
.
.990
105.089
. . 2.022 a. A heterogeneity factor is used. b. Logarithm base = 10.
.
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