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"ABSTRAKThis study aimed to investigate the prevalence of the pfdhps and pfdhfr polymorphisms in southern Somalia. The genetic polymorphisms of both genes were analyzed by nested PCR-RFLP. A total of 150 samples were collected; of these, 101 were shown to be positive for Plasmodium (96 P. falciparum and 5 P. vivax) by nested PCR, the remaining 49 were PCR negative. Of the 96 Plasmodium falciparum isolates, 88 were successfully amplified for pfdhps and pfdhfr polymorphisms. The mutations occurring in the pyrimethamine resistance gene (pfdhfr) at codons 51, 59 and 108 were 59 (67.0%), 51 (58.0%) and 83 (94.3%) isolates, respectively. Sulfadoxine resistance-associated mutations in the pfdhps gene at codons 437, 540 and 581 were found in 41 (46.6%), 43 (48.9%) and 13 (14.8%) samples, respectively. The analysis of pfdhfr and pfdhps combination revealed that 27 (30.7%) isolates harbor the quintuple mutations (I51 R59 N108 - G437 E540 A581 and I51 R59 N108 - G437K540G581). The prevalence of single mutation, triple mutations, quadruple mutations and double mutations haplotypes were 19.3%, 18.2%, 15.9% and 12.5%, respectively. Additionally, sextuple mutations were observed at 2 isolates (2.3%). This study shows that the pfdhfr/pfdhps mutant alleles have moderately declined compared to a previous study, but still remain high. "

"Trimetoprim-sulfametoksazol (TMP/SMX) merupakan golongan antibiotik lini pertama yang digunakan untuk pengobatan infeksi saluran kemih. Antibiotik TMP/SMX bekerja dengan menghambat reaksi enzimatik sintesis folat bakteri pada dua tahap yang berurutan pada bakteri, sehingga kombinasi obat ini dapat memberikan efek sinergi. Gen dfr dan gen sul merupakan gen yang mengkode DHFR dan DHPS yang terdapat di Mobile Genetic Element (MGE) yang keberadaannya dapat meningkatkan kejadian resistensi bakteri terhadap antibiotik trimetoprim-sulfametoksazol. 8 isolat Escherichia coli diketahui resitensi terhadap trimetoprim-sulfametoksazol secara fenotipik diperiksa keberadaan MGE dfr1, dfr5, dfr7&17, sul1 dan sul2 melalui metode PCR konvensional, dilanjutkan dengan analisis asam amino untuk melihat ada atau tidaknya mutasi. 7 dari 8 isolat Escherichia coli yang reistensi antibiotik trimetoprim-sulfametoksazol memiliki MGE dfr dan sul yang berkesesuaian dengan fenotipik resistensi trimetoprim- sulfametoksazol. Mutasi asam amino dijumpai pada gen dfr1 isolat no 95 pada posisi I55V; D64S; N65D; I70V; N129S. dfr5 Isolat nomor 14, 53, 88 dan 95 memiliki jumlah mutasi asam amino sebanyak 10 titik pada posisi: A17G; A20S; D21N; N22D; I26V; P29Q; Y36D; Y37D; L41F; D43G. sedangkan gen sul2 isolat 14, 29, 78, 79 dan 88 mutasi pada posisi G8W dan I12M. Keberadaan MGE dfr dan sul pada isolat klinis menunjukkan adanya mekanisme resistensi ekstrinsik bakteri yang memerlukan perhatian khusus terhadap peningkatan kejadian resistensi bakteri.

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Trimethoprim-sulfamethoxazole (TMP/SMX) is a class of first-line antibiotics used for the treatment of urinary tract infections. TMP/SMX antibiotics work by inhibiting the enzymatic reaction of bacterial folate synthesis at two successive stages in bacteria, so that this drug combination can provide a synergistic effect. The dfr gene and sul gene are genes that code for DHFR and DHPS found in the Mobile Genetic Element (MGE) whose presence can increase the incidence of bacterial resistance to the antibiotic trimethoprim-sulfamethoxazole. 8 isolates of Escherichia coli known to be resistant to trimethoprim-sulfamethoxazole phenotypically examined for the presence of MGE dfr1, dfr5, dfr7&17, sul1 and sul2 through conventional PCR methods, followed by amino acid analysis to see the presence or absence of mutations. 7 of the 8 isolates of Escherichia coli that were trimetoprim-sulfamethoxazole antibiotic retention had MGE dfr and sul corresponding to the phenotypic resistance of trimethoprim-sulfamethoxazole. Amino acid mutations were found in the dfr1 gene isolate no 95 at position I55V; D64S; N65D; I70V; N129S. dfr5 Isolates number 14, 53, 88 and 95 have a number of amino acid mutations of 10 points at position: A17G; A20S; D21N; N22D; I26V; P29Q; Y36D; Y37D; L41F; D43G. while the sul2 gene isolates 14, 29, 78, 79 and 88 mutations at the G8W and I12M positions. The presence of MGE dfr and sul in clinical isolates suggests the existence of a mechanism of bacterial extrinsic resistance that requires special attention to the increased incidence of bacterial resistance."

"Over the past decade, antimalarial drug resistance has rapidly become a major public health problem in South East Asia region including South Sumatra. This study aimed to determine the extent of gene polymorphisms associated with chloroquine resistance (CQR) in P. falciparum isolates from Lahat, Sekayu, Baturaja and Palembang district.Methods: A molecular study was conducted to identify the mutant alleles of the genes associated with the resistance to chloroquine among the isolates of Plasmodium falciparum from South Sumatera. Blood from 25 patients was collected, DNA was isolated, and the sequences of two different genes (Plasmodium falciparum chloroquine resistance transporter/pfcrt and Plasmodium falciparum multidrug resistance/pfmdr1) were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results: This study identified polymorphism in the pfcrt 76-Thr in all isolates and pfmdr1 86-Tyr. These findings may reflect the failure of treatment with the standard dose of chloroquine within the last few years in South Sumatera.Conclusion: PCR-RFLP technique provide a simple and rapid method of detecting polymorphisms in genes that may predict chloroquine resistance (CQR). Although the identification of the polymorphism in the pfcrt and pfmdr1 genes provides a significant indicator of CQR, further studies are needed to determine the role of these polymorphisms in the in vivo and in vitro responses to drug treatment."

"Plasmodium falciparum menggunakan protein EBA140 sebagai salah satu protein yang berperan pada proses invasi ke dalam sel darah merah. Polimorfisme domain F1 gen EBA-140 diketahui memengaruhi spesifisitas perlekatan protein EBA-140 pada reseptor di permukaan sel darah merah. Variasi tipe alel Gerbich pada gen GYPC yang merupakan reseptor bagi EBA-140 juga dapat memengaruhi kemampuan protein ligan EBA-140 dalam berikatan dengan reseptor GYPC di permukaan sel darah merah. Penelitian mengenai keragaman sekuens asam amino domain F1 gen EBA-140 dan variasi alel Gerbich gen GYPC telah dilakukan terhadap 18 isolat klinis P. falciparum yang berasal dari kabupaten Bangka Barat (n = 5), kabupaten Bangka Tengah (n = 4), dan kabupaten Mimika (n = 9). Amplifikasi gen EBA-140 dari isolat parasit malaria dilakukan dengan teknik Polymerase Chain Reaction (PCR). Selanjutnya fragmen DNA parasit diperbanyak dengan metode kloning ke dalam sel bakteri Escherichia coli. Analisis hasil sekuens asam amino domain F1 menunjukkan adanya 7 haplotipe gen EBA-140 dari ketiga daerah tersebut. Tiga haplotipe yaitu ISTK, DSTK, dan ISRE merupakan haplotipe baru yang belum pernah dilaporkan sebelumnya. Analisis variasi alel Gerbich pada gen GYPC menunjukkan tidak ada delesi ekson 3 pada gen GYPC pada ketiga daerah tersebut. Informasi mengenai keragaman haplotipe gen EBA-140 dan gen GYPC dapat dijadikan sebagai acuan dalam mendesain vaksin berbasis gen EBA-140 yang efektif memberantas P. falciparum di Indonesia.

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Plasmodium falciparum utilizies the EBA140 as one of its proteins to invade the red cells. Polymorphisms at the domain F1 of EBA-140 gene have been known to affect the ligand recognition to its corresponding protein receptors glycophorin C (GYPC) or Gerbich antigen. Deletion on the GYPC gene, known as Gerbich blood-type, is known to prevent the parasite invasion using this pathway. Polymorphisms on the GYPC gene could alter the ability of EBA-140 ligand to bind to GYPC receptor on the surface of erythrocyte. Plasmodium falciparum clinical isolates from West Bangka (n = 5), Central Bangka (n = 4), and Mimika regencies (n = 9) were studied for their EBA-140 and GYPC gene polymorphisms. Parasite DNA was amplified using Polymerase Chain Reaction (PCR) and subsequently cloned into Escherichia coli.

Amino acid sequence analysis of the F1 domain showed that there were seven haplotypes of EBA-140 gene from all locations. Three haplotypes of EBA-140 (ISTK, DSTK, ISRE) detected in this study were new haplotypes that had not been reported previously. Analysis on the Gerbich allele detected no exon 3 deletion on the GYPC gene from all location. These findings provide useful information if the vaccine involving the EBA-140 component would be developed."

"Sejalan dengan semakin tingginya resistensi terhadap obat antimalaria dalam klinis, terdapat kebutuhan dilakukan pencarian senyawa-senyawa kimia yang berpotensi. Metode komputasi digunakan untuk membantu pencarian karena memiliki keunggulan seperti tidak banyak mengeluarkan biaya dan dapat dipercaya memprediksi afinitas ikatan ligan dengan target obat (protein). Tujuan penelitian adalah untuk mendapatkan senyawa analog triklosan dan senyawa herbal Indonesia yang berpotensi sebagai antimalaria. Analog triklosan dan beberapa senyawa basis data herbal Indonesia dihitung afinitas ikatannya dengan metode Molecular Mechanics Poisson-Blotzmann Surface Area (MM-PBSA) pada Plasmudium falciparum Enoyl Reductase(PfENR), dengan tiga titik variabel suhu 27oC, 37oC, dan 39oC. Didapatkan nilai energi bebas Gibbs (ΔG) pada analog triklosan enansiomer 1b -18,5009 kkal/mol suhu 37oC dan pada senyawa herbal spinasterol -31,3435 kkal/mol suhu 37oC dan limasin -24,9885 kkal/mol suhu 37oC. Dengan nilai energi bebas Gibbs tersebut menunjukkan bahwa senyawa tersebut memiliki potensi sebagai antimalaria.

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Keeping pace with emerging drug resistance in clinically important pathogens will be greatly aided by inexpensive yet reliable computational methods that predict the ligands binding affinities for drug targets. the aim of this study to obtain potention antimalaria from analogues triclosan compound and Indonesia herbal compound. Analogues triclosan and several compound from Indonesia herbal database form Indonesia be calculated with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) for the Plasmodium falciparum Enoyl Reductase (PfENR), at three point variable of temperature 27oC, 37oC, and 39oC. Obtained Gibbs free energy (ΔG) for analogues triclosan enansiomer 1b -18,5009 kkal/mol 37oC and for herbal compound spinasterole -31,3435 kkal/mol 37oC dan limacine -24,9885 kkal/mol 37oC. With that Gibbs free enrgy enansiomer 1a, spinasterole, and limacine shows that compound have potention as antimalaria."

"The invention of graphical processing units (GPUs) has significantly improved the speed of long processes used in molecular dynamics (MD) to search for drug candidates to treat diseases, such as malaria. Previous work using a single GTX GPU showed considerable improvement compared to GPUs run in a cluster environment. In the current work, AMBER and dual GTX 780 and 970 GPUs were used to run an MD simulation on the Plasmodium falciparum enoyl-acyl carrier protein reductase enzyme; the results showed that performance was improved, particularly for molecules with a large number of atoms using single GPU."

"Latar belakang: Sampel P. falciparum dari lapangan dapat menampilkan bentuk dan jenis yang bervariasi. Penelitian ini bertujuan mengetahui keragaman alel MSP-1 blok 2 isolat P. falciparum yang berasal dari daerah pegunungan dan daerah pantai Sumatera Barat, Indonesia dan membandingkan keberadaan jenis-jenis alel dari kedua daerah pegunungan dan pantai. Metode: 56 sampel darah yang terinfeksi P. falciparum, diperoleh dari 27 penderita yang berobat pada Puskesmas di Kabupaten Solok Selatan yang merupakan daerah pegunungan dan 29 penderita yang datang berobat pada Puskesmas dari daerah pantai di kabupaten Pesisir Selatan, Sumatera Barat, Indonesia. Daerah-daerah yang mengapit sifat-sifat yang sangat polimorfi k, blok 2 MSP-1, ditentukan genotipnya melalui allele-specifi c nested PCR guna menganalisa populasi kepadatan parasit. Analisis urutan daerah-daerah polimorfi k dari MSP-1 juga dilakukan untuk mengidentifi kasi keanekaragaman alel di dalam populasi parasit. Hasil: Polimorfi sme alel yang beranekaragam dari MSP-1 diidentifi kasi pada isolat P. falciparum dari suatu daerah pegunungan dan daerah pantai di Sumatera Barat, Indonesia, dan kebanyakan infeksi ditemukan berupa infeksi campuran. Analisa urutan MSP-1 blok 2 mengungkapkan bahwa teridentifi kasi 16 alel berbeda untuk MSP-1 (3 untuk tipe K1, 2 untuk tipe MAD20 dan 2 untuk tipe RO33). Kesimpulan: Dari isolat lapangan P. falciparum yang dikumpulkan dari suatu daerah pegunungan dan daerah pantai di Sumatera Barat teridentifi kasi polimorfi fme genetik yang luas. Juga ditemukan tingkat infeksi campuran yang tinggi, sebagai derajat kemajemukan infeksi yang tinggi.

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Background: The fi eld isolates of P. falciparum may display variant forms and different frequencies. This study was designed to know the diversity of allelic type of MSP-1 block 2 among P. falciparum isolates collected in a mountain and a coastal area in West Sumatera, Indonesia, and compare mountain and coastal area.

Methods: A total of 56 P. falciparum infected blood samples, collected from 27 patients attending local health facilities in South Solok district in a mountain region and 29 patients attending a local health facilities in South Coastal district region, West Sumatera, Indonesia were used in this study. The regions fl anking the highly polymorphic characters, block 2 for MSP-1, were genotyped by allele-specifi c nested-PCR to analyse the population diversity of parasite. Sequence analysis of the polymorphic regions of MSP-1 was also conducted to identify allelic diversity in the parasite population.

Results: Diverse allelic polymorphism of MSP-1 was identifi ed in P. falciparum isolates from a mountain area and a coastal area in West Sumatera, Indonesia, and most of the infections were determined to be mixed infections. Sequence analysis of MSP-1 block 2 revelaled that 16 different alleles for MSP-1 (3 for K1 type, 2 for MAD20 type and 2 for RO33 type) were identified.

Conclusion: Extensive genetic polymorphism with diverse allele type was identifi ed in MSP-1 in P. falciparum fi eld isolates from a mountain and a coastal area. A high level of mixed infections was also obcserved, as was a high degree of multiplicity of infection."

"Latar belakang. Meningkatnya kasus HIV-AIDS human immunodeficiency virus-acquired immunodeficiency syndrome secara global memicu kewaspadaan akan peningkatan infeksi oportunistik, salah satunya infeksi Pneumocystis jirovecii yang mengakibatkan pneumonia PjP. Infeksi PjP merupakan kasus yang sulit ditangani terkait rendahnya sensitivitas uji diagnostik diiringi dengan peningkatan kasus resistensi terhadap antibiotik. Di Indonesia belum terdapat data demografis, epidemiologi molekuler maupun data resistensi mengenai kasus infeksi PjP. Mengantisipasi masalah tersebut, dalam penelitian ini dikembangkan uji diagnostik PjP pada ODHA Orang Dengan HIV-AIDS terduga pneumonia melalui pendekatan molekular terhadap gen MSG Major Surface Glycoprotein disertai dengan karakterisasi gen DHPS dihidropteroat sintase dan gen mtLSU mitochondrial large subunit yang berkorelasi dengan genotipe resisten dan virulensi P. jirovecii. Tujuan penelitian. Memperoleh suatu uji deteksi infeksi PjP, data genotipe resistensi dan virulensi PjP melalui pendekatan secara molekuler yang dapat dimanfaatkan sebagai dasar data demografi dan epidemiologi molekuler PjP di Indonesia. Metode penelitian. Pengembangan uji diagnosis molekuler PjP terhadap gen MSG dilakukan dengan metode real- time PCR yang diujikan terhadap 100 sampel sputum. Pola genotipe resistensi dilakukan melalui amplifikasi gen DHPS dilanjutkan dengan restriction fragment length polymorphism RFLP . Virulensi daerah hot spot gen mtLSU dianalisis dengan metode PCR dan sekuensing DNA. Hasil. Secara demografi, diketahui prevalensi PjP pada ODHA terduga pneumonia di Jakarta mencapai 20,0, laki-laki 75, rentang usia terbanyak 31-40 tahun 35, dominan 80 pada kisaran sel limfosit T CD4 200-349 sel/L. Sebanyak 12 pasien menunjukkan gen DHPS positif, lima pasien 41,66 merupakan genotipe wild type WT dan 7 pasien lainnya 58,32 merupakan genotipe resisten, terdiri dari 16,67 genotipe-3 dan 41,66 genotipe campuran WT dan genotipe 1. Analisis virulensi berdasarkan gen mtLSU diperoleh 30 strain PjP positif yang didominasi oleh variasi-3. Status imun pasien lebih berkaitan dengan genotipe resistensi dibandingkan dengan jenis varian. Kesimpulan. Uji real-time PCR yang dikembangkan mampu memberikan nilai diagnostik yang lebih baik dibandingkan pewarnaan Giemsa. Terdapat 3 genotipe gen resistensi WT, genotipe 1 dan 3 dan 7 varian P. jirovecii yang bersirkulasi di Jakarta. Genotipe resistensi lebih berkaitan terhadap kondisi klinis pasien dibandingkan dengan jenis varian.

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Background. The global rise of HIV-AIDS cases increase the alertness against oportunistic infections, one of them is Pneumocystic jirovecii pneumonia PjP. PjP infection is a one of a tough infection to be cured due to low sensitivity of its diagnostic method following the escalation of PjP resistance against antibiotics. There is no demografic, molecular epidemiology nor antibiotics resistance data were available related to PjP infection in Indonesia. Thus, this study was conducted to develop a molecular test to diagnose PjP infection in HIV-AIDS suspected pneumonia patients based on MSG Major Surface Glycoprotein gene detection, followed by characterization of DHPS dihydropteroat syinthetase and mtLSU mitochondrial large subunit genes represent genoype resistance and P. jirovecii virulence. Research objective. To obtain a molecular test in diagnosing PjP infection and information of P. jirovecii genotype resistance and virulence based on molecular characteristics, which can be used further as demographic and molecular epidemiology basis data of PjP in Indonesia. Research methods. Molecular diagnostic test aimed for MSG gene of P. jirovecii detection was done through real-time PCR against 100 sputum samples. Genotype resistance and P. jirovecii polymorphism patterns was done through DHPS and mtLSU genes amplification followed by restriction fragment length polymorphism RFLP and DNA sequencing analysis. Virulence of the hot spot area are of the mtLSU gene was analyzed by PCR method and DNA sequencing. Results. The prevalence of PjP infection in HIV-AIDS suspected pneumonia patients in Jakarta was 20.0, male 75 within 31-40 y.o 35, dominant 80 from patients with CD4 T-lymphocytes of 200-349 cells/L. Molecular real-time PCR methods give five times sensitivity higher than Giemsa stain. Twelve patients showed positive DHPS gene, five patients 41.67 were wild type WT genotypes and 7 other patients 58.32 were resistant genotypes, with 16.66 was genotype-3 and other 41.66 was mixed genotypes WT and genotype 1. Virulence analysis based on mtLSU gene show 30 positive strains which dominated by variant-3. The patients immune status is more related to the resistance genotype compared to the variant type. Conclusion. The developed real-time PCR method is proven to able to give better diagnostic value than Giemsa stain. There are 3 genotypes of resistance genes WT, genotypes 1 and 3 and 7 variants of P. jirovecii circulating in Jakarta. Resistance genotypes are more related to the clinical condition of patients compared to variant types. "

"Malaria merupakan salah satu infeksi parasit yang menjadi permasalahan di dunia. Tidak adanya vaksin yang efektif dan strain Plasmodium yang resisten terhadap obat antimalaria menunjukkan pentingnya untuk adanya pengembangan agen kemoterapi baru. Metode yang saat ini sedang banyak dikembangkan adalah pencarian obat antimalaria dengan menggunakan penapisan in silico atau dikenal pula dengan nama virtual screening. Salah satu enzim yang berperan dalam perkembangan parasit malaria adalah Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibisi pada enzim tersebut akan menyebabkan biosintesis lemak tipe II pada parasit akan terhenti. Pada penelitian kali ini dilakukan penapisan in silico menggunakan perangkat lunak GOLD untuk mencari kandidat inhibitor PfENR dengan menggunakan ligan yang terdapat pada database Tanaman Obat di Indonesia. Pada perangkat lunak GOLD dilakukan penambatan molekuler antara ligan dengan makromolekul target yaitu PfENR. Target ini telah dioptimasi dengan penghilangan residu dan penambahan muatan. Ligan diharapkan dapat menjadi inhibitor PfENR. Berdasarkan hasil dari penapisan in silico ini terdapat 5 kandidat senyawa inhibitor yang diharapkan dapat dikembangkan sebagai obat antimalaria. Senyawa tersebut yaitu Kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside, Cyanidin 3,5-di-(6-malonylglucoside), 8-Hydroxyapigenin 8-(2'',4''-disulfatoglucuronide), Epigallocatechin 3,5,-di-O-gallate, dan Quercetin 3,4'-dimethyl ether 7-alpha-L-Arabinofuranosyl-(1-6)-glucoside dengan kisaran GoldScore dari 80,6236 sampai 100,4109.

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Malaria is one of problematic infectious diseases worldwide. The absence of an effective vaccine and the spread of drug resistant strains of Plasmodium clearly indicate the necessity for the deveploment of new chemotherapeutic agents. Recent method being developed is searching a new drug of antimalarial using in silico screening, or also known as virtual screening. One of enzyme target that important for growth of the malaria parasite is Plasmodium falciparum Enoyl Acyl Carrier Protein Reductase (PfENR). Inhibition of this enzyme cause the fatty acid biosynthesis type II will be terminated. In this research, in silico screening was performed using GOLD software to find inhibitor candidates of PfENR by using ligands from the database of Medicinal Plants in Indonesia. On the GOLD software moleculer docking experiments were performed between ligands and macromolecule target PfENR. This target that has been optimized with residue removal and charges addition. Ligand is expected to be the PfENR inhibitors. Based on the results obtained from the in silico screening there were 5 inhibitor candidates which expected to be developed as an antimalarials. These compounds were Kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside, Cyanidin 3,5-di-(6-malonylglucoside), 8-Hydroxyapigenin 8-(2'',4''-disulfatoglucuronide), Epigallocatechin 3,5,-di-O-gallate, and Quercetin 3,4'-dimethyl ether 7-alpha-L-Arabinofuranosyl-(1-6)-glucoside with the GoldScore ranged from 80.6236 to 100.4109."

"ABSTRAKMalaria menjadi masalah kesehatan global utama dengan angka kejadian kemoresistensi yang tinggi, sedangkan ketersediaan obat yang efektif terbatas. Hal tersebut mendasari pentingnya pengembangan obat antimalaria baru. Pendekatan berbasis struktur digunakan untuk merancang analog triklosan dengan target enzim Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Gugus fenol disubstitusi dengan gugus metoksi, serta gugus Cl di posisi 2? cincin B dimodifikasi menjadi gugus 2,3-dihidroksi-propionamida. Penambahan dua gugus hidroksi pada cincin B menggunakan metode dihidroksilasi asimetrik Sharpless dengan ligan kiral (DHQ)2PHAL dan (DHQD)2PHAL menghasilkan dua produk analog triklosan sebagai campuran enansiomer. Interaksi molekuler analog triklosan terhadap PfENR ditentukan dengan AutoDock. Campuran enansiomer yang dihasilkan dari ligan kiral (DHQ)2PHAL memiliki rotasi spesifik (+) 0,0833, sedangkan campuran enansiomer yang dihasilkan dari ligan kiral (DHQD)2PHAL memiliki rotasi spesifik (-) 0,0678. Nilai IC50 kedua analog triklosan ditentukan terhadap galur sensitif klorokuin, 3D7. Jumlah parasit dihitung secara mikrokopis melalui apusan darah tipis yang diwarnai Giemsa. Nilai IC50 ditentukan dengan membandingkan parasitemia senyawa uji dengan kontrol yang dianggap memiliki pertumbuhan 100%. Aktivitas antimalaria campuran enansiomer yang dihasilkan dengan (DHQ)2PHAL dan dengan (DHQD)2PHAL memperlihatkan aktivitas yang lebih poten dibandingkan triklosan (IC50 2,72 x 10-2 M), dengan IC50 berturut-turut 3,38 x 10-5 M dan 2,82 x 10-5 M.

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ABSTRACTMalaria is a major global public health problem that alarming spread of drug resistance and limited number of effective drugs. That reason underline how important it is to discover new antimalarial drug. A structure-based approach has been taken to develop substituted analogs of triclosan that target the key malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). The phenol moiety was chemically substituted with methoxy group, and Cl group at posistion 2? in ring B also modified with 2,3-dihydroxy-propionamide group. Sharpless asymmetric dihydroxylation with chiral ligand (DHQ)2PHAL and (DHQD)2PHAL is used to introduce two hydroxyl groups into the ring B to give two analogs of triclosan as enantiomer mixture. The binding energies of two analogs for PfENR were determined using Autodock. The enantiomer mixture generated by chiral ligand (DHQ)2PHAL showed specific rotation of (+) 0,0833, while enantiomer mixture resulted from chiral ligand (DHQD)2PHAL have (-) 0,0678 of specific rotation. The IC50 of two analogs of triclosan were determined against Plasmodium falciparum chloroquin-sensitive strain, 3D7. The number of parasites on thin Giemsa stained smears was calculated microscopically. IC50 determined by comparing paracitemia parasite growth in the presence of compound with that of control without compound. The analog compounds, enantiomer mixture resulted by either (DHQ)2PHAL or (DHQD)2PHAL showed a higher antimalarial activity than triclosan (IC50 2,72 x 10-2 M), with IC50 3,38 x 10-5 M and 2,82 x 10-5 M, respectively."