Mustofa Mustofa
Department Of Pharmacology & Therapy, Faculty Of Medicine, Public Health, And Nursing, Universitas Gadjah Mada, Jalan Farmako, Sekip Utara, Yogyakarta 55281, Indonesia

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In vitro anticancer activity of N-benzyl 1,10-phenanthroline derivatives on human cancer cell lines and their selectivity Eti Nurwening Sholikhah; Jumina Jumina; Sitarina Widyarini; Ruslin Hadanu; Mustofa Mustofa
Indonesian Journal of Biotechnology Vol 23, No 2 (2018)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.33997

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This research was conducted to evaluate the anticancer activity of new compounds of benzyl-1,10- phenanthroline derivatives and their selectivity. In vitro anticancer activity of 11 benzyl-1,10-phenanthroline derivatives were conducted on three human cancer cell lines, cervical cancer (HeLa), myeloma (NS-1), and breast cancer (MCF-7) using MTT-based cytotoxicity assay. The cytotoxicity of each compound was assessed to normal Vero cell line by the same method. The in vitro anticancer activity and cytotoxicity was expressed by the concentration inhibiting 50% of the cell growth (IC50), and the selectivity index (SI) was determined by calculating ratio of the IC50 on Vero cell line and the human cancer cell lines. The results showed that among the 11 compounds tested, the (1)-N-(4-butoxybenzyl)-1,10-phenanthrolinium bromide exhibited the best in vitro anticancer activity with an IC50 27.60 ± 2.76 µM on HeLa, 6.42 ± 5.53 µM on NS-1 and 9.44 ± 2.17 µM on MCF-7 cell lines. Its SI were 377.65 ± 39.97 on HeLa, 6158.72 ± 5306.34 on NS-1 and 1140.11 ± 261.85 on MCF-7 cell lines. This study demonstrated that (1)-N-(4-butoxybenzyl)-1,10-phenanthrolinium bromide possessed a potential in vitro anticancer activity on cancer cell lines with high selectivity
Association of hydrazine and SGPT level two hours after drug administration at the end of intensive phase treatment of pulmonary tuberculosis patients Ave Olivia Rahman; Jarir At Thobari; Mustofa Mustofa
Tropical Medicine Journal Vol 2, No 2 (2012): Tropical Medicine Journal
Publisher : Pusat Kedokteran Tropis

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (385.192 KB) | DOI: 10.22146/tmj.17124

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ABSTRACTIntroduction: Isoniazid in the regiment treatment of pulmonary tuberculosis patients causes side effects. Hepatotoxicity is one of the isoniazid’s side effects that need medical attention. Isoniazid-induced hepatotoxicity has no correlation with high level of isoniazid in plasma. However, several animal studies show it has an association with hydrazine, a metabolite of isoniazid. The role of hydrazine in isoniazid-induced hepatotoxicity among tuberculosis patients is unclear.Objective: The aim of this study was to analyze the correlation of hydrazine and serum glutamic-pyruvic transaminase (SGPT) levels at two hours after drug administration in the end of intensive phase treatment of pulmonary tuberculosis patients.Methods: This was an observational study with cross-sectional design. Fifty eight newly diagnosed pulmonary tuberculosis patients were enrolled in this study. Venous blood sampling was collected at two hours after drug administration in the end of intensive phase treatment. SGPT level was measured by an automatic chemical analyzer. Hydrazine level was measured by using high-performance liquid chromatography (HPLC). Statistical significance was analyzed using correlation test.Results and Discussion: The incidence of hepatotoxicity was 3.4% and about 8.6% patients had elevated SGPT at two hours after drug administration in the end of intensive phase treatment. There was no correlation between hydrazine level and SGPT levels in this study. These results indicated that hepatotoxicity or minimal liver damage in some patients might occur in the administration of standard dose isoniazid. It might be caused by isoniazid’s metabolites itself, or various other factors.Conclusions: There was no correlation between hydrazine level and SGPT levels at 2 hours after drug administration in the end of intensive phase treatment in this study.
Ketersediaan Obat Esensial pada Sarana Kesehatan di Kabupaten Bangka Barat Achmad Nursyandi; Mustofa Mustofa; Mubasysyir Hasanbasri
Jurnal Kebijakan Kesehatan Indonesia Vol 1, No 3 (2012)
Publisher : Center for Health Policy and Management

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (318.057 KB) | DOI: 10.22146/jkki.v1i3.36017

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Background: The effectiveness of treatment at government health facilities is largely determined by the availability of the drug. In addition to essential drugs, doctors and the public can choose medications that are considered more suitable for medical needs. Bureaucratic rigidity and lack of funds the government plans to make the supply of medicines in health centers to be minimalist in terms of number and variety of drugs. Such inflexibility encourage minimalist prescribing behavior among primary care physicians and health workers. Objective: This study want to learn management practices that deal with drug supply and its distribution in government owned primary health care facilities. It specifically tried to identify strategies at health center level that allow the provision of more drugs in accordance with the medical needs and rational drug use practices. Method: Data were collected by observation report drug use and demand for health facilities in January-June 2010 and in- depth interview of chief health official, the head of pharmacy department, 7 of pharmacy main health centers and 11 midwives/nurses extending health center, village health clinic and village health post. Results: This case illustrates a successful story about making drugs available at primary health care facilities. Five main health centers, four extending health centers, and ten village health clinic and village health posts are classified as “safe” based on MOH standard. This success reflects human resource capacity and decentralized management of drug supply. Pharmacists and pharmacy assistants throughout the Bangka Barat Regency has already trained in drug supply management. The study also found that the procurement of drugs has been based on bottom-up planning. Although under the coordination of district level pharmacy unit, health care centers has broader authority to determine their drug needs. They also have their own drug procurement budget that are part of district budget that can be used for unexpected situations. Conclusion: This study attempted to show effort to change local government health sector bureaucracy in decentralization era. This case study shows the involvement and bigger participation of primary care facilities in the planning and implementation of drug supply. Health centers have a greater authority in managing the medication needs to circumstances beyond expectations. Communication, information and education to doctors about the drug delivery mechanism will allow doctors to prescribe drugs according to the medical needs of patients and drug development, and because it makes health care facilities into place an effective treatment. Latar Belakang: Efektivitas pengobatan di fasilitas kesehatan pemerintah sangat ditentukan oleh ketersediaan obat. Di samping obat esensial, dokter dan masyarakat dapat memilih obat-obat yang dipandang lebih cocok untuk kebutuhan medik. Kekakuan birokrasi perencanaan dan keterbatasan dana pemerintah membuat penyediaan obat di puskesmas menjadi minimalis dari sisi jumlah dan variasi obat. Kekakuan seperti itu mendorong praktik peresepan minimalis yang diragukan manfaat terapetiknya. Tujuan: Penelitian ini mempelajari manajemen penyediaan obat dan distribusinya di fasilitas kesehatan dasar. Ia secara khusus berusaha menemukan strategi-strategi di tingkat puskesmas yang membuat penyediaan obat lebih sesuai dengan kebutuhan lapangan dan pengobatan rasional. Metode: Data dikumpulkan dengan observasi laporan pemakaian dan permintaan obat sarana kesehatan bulan Januari-Juni 2010 dan wawancara mendalam terhadap kepala dinas kesehatan, kepala instalasi farmasi, 7 pengelola obat puskesmas dan 11 bidan/perawat pustu, polindes serta poskesdes. Hasil: Penelitian ini menunjukkan bahwa lima puskesmas, empat puskesmas pembantu, dan sepuluh polindes dan poskesdes berhasil merencanakan dan menyediakan obat hingga pada tingkat yang “aman”. Keberhasilan ini merupakan bukti dari kapasitas tenaga yang memadai. Apoteker dan seluruh pengelola obat puskesmas Kabupaten Bangka Barat sudah memiliki mengikuti pelatihan manajemen pengelolaan obat. Penelitian juga menemukan bahwa pengadaan obat telah berbasis desentralisasi dan mencerminkan perencanaan bottom up. Meski di bawah koordinasi instalasi farmasi kabupaten, puskesmas memiliki kewenangan menentukan kebutuhan. Mereka juga memiliki fleksibilitas pengadaan obat sendiri untuk situasi di luar dugaan. Kesimpulan: Penelitian ini berusaha memperlihatkan upaya perubahan birokrasi di bidang kesehatan dalam era desentralisasi. Studi kasus dalam penyediaan obat esensial di Kabupaten Bangka Barat menunjukkan keterlibatan dan partisipasi puskesmas yang lebih besar dalam perencanaan dan implementasinya. Puskesmas juga memiliki kewenangan lebih besar dalam mengelola kebutuhan obat untuk situasi di luar dugaan. Komunikasi, informasi dan edukasi kepada dokter tentang mekanisme penyediaan obat akan memudahkan dokter meresepkan obat sesuai dengan kebutuhan medik pasien dan perkembangan obat, dan karena itu membuat fasilitas kesehatan menjadi tempat pengobatan yang efektif.
Synergistic interaction between quercetin and doxorubicin on MCF-7 human breast cancer cell line Abdul Khairul Rizki Purba; . Mustofa; Indwiani Astuti
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 45, No 03 (2013)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (322.697 KB) | DOI: 10.19106/JMedScie004503201303

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The effectiveness of doxorubicin has decreased due to resistance of cancer cells. One of thenatural ingredients that are proven to reduce the resistance to anticancer is quercetin. Quercetininteracts with doxorubicin via a competition of P-glycoprotein (P-gp) transporter activity. Theaim of this study is to evaluate the interaction of quercetin and doxorubicin as cytotoxicityeffect on MCF-7 cells. Cytotoxicity test was conducted by the MTT method. Mechanism ofinteraction between doxorubicin and quercetin was evaluated with isobologram analysis.Doxorubicin and quercetin inhibited the growth of MCF-7 cells significantly. Doxorubicin andquercetin respectively had IC50 of 21M and 103 M. The interaction of doxorubicin and quercetinwere characterized by the amount of doxorubicin IC50 equivalent and quercetin IC50 equivalentless than 1 and the point-intercept of each IC50 notation equivalent plotted on the graph belowthe additive line. Analysis of isobolograms indicated that the interaction doxorubisn and quercetinin each of the ratios had synergy. Quercetin can be considered to be in a combination wit
Cytotoxicity of α-terpineol in HeLa cell line and its effects to apoptosis and cell cycle Rasuane Noor; Indwiani Astuti; . Mustofa
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 46, No 01 (2014)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (649.907 KB) | DOI: 10.19106/JMedScie004601201401

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α-Terpineol is a natural compound of terpenoid alcohols class. However, it can be synthesizedfrom α-pinene of turpentin content. α-Terpineol has been reported as potential anticancer agentdue to its activity on inhibition of cells growth and induction of tumor cell death. However, itsanticancer activity in HeLa cervical cancer cells line has never been studied, yet. The aim of thisstudy was to evaluate the cytotoxicity of α-terpineol and its effects to apoptosis and cell cycle.This was a quasi-experimental study with post-test only with non-equivalent control groupdesign. Cytotoxicity of á-terpineol was evaluated using MTT cell viability assay. The effect of α-terpineol on cell apoptotis was tested using acridine orange-ethidium bromide staining method,whereas its effect on cell cycle was evaluated by flowcytometry method. The results showedthat α-terpineol had cytotoxicity against HeLa cell with an IC50 value about 12.46 μg/mL.Furthermore, α-terpineol induced the HeLa with an IC50 value about 13.12 μg/mL. Cell accumulationat G1 phase during cell cycle after incubation with α-terpineol (52.78)was observed. In conclusion,α-terpineol is potential as an anticancer due to its ability to induce cell apoptosis and to inhibitthe cell cycle at G1 phase.
Antimicrobial activity of bioactive compounds isolated from Swietenia mahagoni (L) Jacq. against Staphylococcus aureus and Pseudomonas aeruginosa Handry Darussalam,; Titik Nuryastuti; . Mursiti; . Mustofa
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 46, No 04 (2014)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (107.331 KB) | DOI: 10.19106/JMedScie004604201402

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Widespread bacterial resistance has led to more difficult to treat infectious diseases with availableantibiotics. Therefore, new antibiotics are needed face of the growing antibiotic resistance. Swieteniamahagoni (L.) Jacq. is one of potential medicinal plants as a source new antibiotics. Five compoundshave been isolated from an ethanolic extract of S. mahagoni (L.) Jacq., however its antimicrobialactivity has not been investigated, yet. This study was conducted to evaluate the antimicrobialactivity of these compounds. Minimal Inhibitory Concentration (MIC) and Minimal BactericidalConcentration (MBC) were determined against Staphylococcus aureus and Pseudomonas aeruginosastrains. Among five compounds tested, compound 3 (3,4,5,6,7-pentaethyl-1-methoxy-1H-indazole)and compound 4 (5-ethyl-6-methoxymethyl-2-methyl-1,2-dihydropyridine) were found to be activeagainst the bactrial strains tested with the MICs and MBCs values ranged from 50 to 100 μg/mL. Inconclusion, among five compounds isolated from S. mahagoni (L.) Jacq., compound 3 and 4showed moderate antimicrobial activity against S. aureus and P. aeruginosa strains.
Ondansetron serum concentration and polymorphisms of CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of chemoterapy induced nausea and vomiting DA Perwitasari; . Mustofa
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 1 (2016)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (407.146 KB) | DOI: 10.19106/JMedSci004801201603

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This study was aimed to understand differences of ondansetron serum concentrationin each antiemetic responses, polymorphisms of 5HT3B receptor, CYP2D6 and ABCB1genes in Indonesian cancer patients treated with high emetogenic cytostatics. We recruitedcancer patients in Dr Sardjito Hospital treated with cisplatin (≥ 50 mg/m 2) as monotherapyor combination therapy. Patients were treated with ondansetron 8 mg intravenously anddexamethasone 8 mg intravenously and metoclopramide (10 mg orally) after cytostaticadministration until 5 days after chemotherapy. We cathegorized the nausea and vomitinggrade according to the National Cancer Institute Common Toxicity Criteria v.3. We alsodetermined some SNPs of ABCB1, 5HT3B and CYP2D6 genes using realtime PCR. Werecruited 191 cancer patients in this study with the average of ondansetron serumconcentration reached 33.48 ng/ml (SD: 18.54). According to the patients’ response tothe antiemetic, during the acute phase, 21.8% patients experienced acute nausea and30.2% patients experienced acute vomiting. Only the haplotype of CTG-CTG of ABCB1which have significant association with ondansetron serum concentration. EM patients ofCYP2D6 and patients with haplotype of delAG of 5HT3B had lower ondansetron serumconcentration. However, IM patients of CYP2D6 showed higher ondansetron serumconcentration and lower grade of nausea and vomiting. Variations of ABCB1, CYP2D6and 5HT3B may be used as pharmacogenetic marker in predicting antiemetic response incancer patients receiving highly emetogenic cytostatic.
Analysis of Enzyme Activity of Alcohol Dehydrogenase and Alcohol Dehydrogenase 3 (ADH3) Gene Polymorphism of Alcoholics and Non-Alcoholics in Indonesia. . Suhartini; . Mustofa; Yudha Nurhantari; Bambang Udji Djoko Rianto
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 48, No 2 (2016)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (766.347 KB) | DOI: 10.19106/JMedSci004802201604

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ABSTRACTAlcohol is an addictive substance that is often misused worldwide, including in Indonesia. Ninety percent of the alcohol that enters the body will be metabolized in the liver using the alcohol dehydrogenase (ADH) enzyme. It is important to determine the activity of ADH enzyme and ADH3 gene polymorphism on alcoholics and non-alcoholics in Yogyakarta, Indonesia. The aim of the study is to determine ADH activity and identify ADH3 gene polymorphism of alcoholics and non-alcoholics in Yogyakarta, Indonesia. This study was an observational study with a cross-sectional design method. Blood samples were taken from 71 Javanese alcoholics and 71 non-alcoholics of Javanese descent in Yogyakarta, Indonesia. The participants were initially requested to sign an informed consent form. Examination of ADH enzyme activity used the spectrophotometry method and ADH3 gene polymorphism was assessed with PCR-RFLP using Ssp I restriction enzyme. The activity of ADH enzyme in all individuals appeared to be a slower type. The average of the ethanol value of alcoholics and non-alcoholics were 0.05554 mM and 0.0758 mM respectively. Gene type of alcoholics were ADH3*2(75.4%), ADH3*1/3*2(21.5%), and ADH3*1(3.1%), and non-alcoholics were ADH3*2(88.6%), ADH3*1/3*2(10.0%), and ADH3*1(1.4%). There were no significant differences between the activity of ADH with polymorphism of ADH3 gene in either alcoholics and non-alcoholics (p>0,05). Conclusion: The activity of ADH enzyme in all participants appeared to be a slower type. Most of the ADH3 gene polymorphism of alcoholics and non-alcoholics were both ADH3*2 (75.4% and 88.6%). There was no differences of ADH enzyme activity with ADH3 gene polymorphism between alcoholics and non-alcoholics of Javanese population in Yogyakarta, Indonesia.
Mechanism of cytotoxic activity of chalcone derivatives against K562 leukemia cell lines Arina Novilla; . Mustofa; Indwiani Astuti; . Jumina; Hery Suwito
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 49, No 4 (2017)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (310.272 KB) | DOI: 10.19106/JMedSci004904201701

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Two chalcone derivatives i.e. (E)-1-(4-aminophenyl)-3-(2,3dimethoxyphenyl)-prop-2-en-1-one (Compound-1), and (E)-1-(4-aminophenyl)-3-phenylprop-2-en-1-one) (Compound-2),has been proven to have potential cytotoxic activity. The aim of this study was toevaluate the effect of these compounds on PI3K/Akt signalling pathway in K562 celllines. After incubation with the tested compounds, AKT, caspase-3, STAT3 and cyclinD1 concentrations were measured using ELISA. Furthermore, cell cycle was analysedusing flowcytometry. Imatinib and isotretinoin were used as positive control, whereascell culture without treatment was used as negative control. The AKT concentration aftertreatment with Compound-1 and -2 was significantly lower than that control, imatiniband isotretinoin (p<0.05). The apoptotic indices after treatment with Compound-1 and-2 were significantly higher than control, however they were lower than imatinib andisotretinoin (p<0.05). The caspase-3 concentration after treatment with Compound-1 at5 and 10 μg/mL and Compound-2 at 10 μg/mL was significantly higher than that controland imatinib, however it was lower than isotretinoin (p<0.05). The STAT3 concentrationafter treatment with Compound-1 and -2 was significantly lower than that control andisotretinoin at 50 μg/mL (p<0.05) and similar with imatinib (p>0.05). The cyclin D1concentration after treatment with Compound-1 and -2 was significantly lower than thatcontrol, imatinib and isotretinoin (p<0.05). In addition, Compound-1 and -2 arrested G0/G1 and G2/M phase in K562 cell lines, with comparable results to imatinib and isotretinoin.In conclusion, the mechanism of cytotoxic activity of Compound-1 and -2 are through thePI3K/Akt signalling pathway inhibition, apoptosis induction by upregulation of apoptoticmarkers, and inhibition of cell cycle progression by regulating cell cycle-related factors.
The SLCO1B1*15 haplotype associated with lower clinical outcome in Indonesian tuberculosis patients Sunarto Ang; Akhmad Kharis Nugroho; Ahmad Hamim Sadewa; Lukman Hakim; . Mustofa
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 1 (2018)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (351.494 KB) | DOI: 10.19106/JMedSci005001201806

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Rifampin is one of first-line drugs for the treatment of tuberculosis. In Indonesia nearly alltuberculosis patients show lower rifampin plasma concentrations possibly due to genetics.Rifampin is a substrate of the organic anion-transporting polypeptide 1B1 (OATP 1B1)encoded by the solute carrier organic anion transporter family member 1B1 (SLCO1B1).This study aimed to identify haplotype polymorphisms of tuberculosis drug transporterswith an impact on clinical outcome in tuberculosis patients. Thirty-six patients from AbdulWahab Sjahranie General Hospital, Samarinda, East Kalimantan were involved in thestudy. Buffy coat from patient blood samples were tested for SLCO1B1 and SLCO1B3polymorphisms by RFLP and ARMS PCR, whereas the clinical outcome was examinedbased on the sputum conversion. The frequency of patients with SLCO1B1*15 haplotypewas 63.9%. The SLCO1B1*15 haplotype was associated with susceptibility to failureof clinical outcome (p=0.005; RR=4.52; 95% CI: 1.22-16.64). The OATP1B1*15haplotype revealed that the failure of clinical outcome was markedly increased comparedto the three other haplotypes. These results suggest that the SLCO1B1*15 haplotypeis an important predisposing factor for lower clinical outcome. Our data indicate thatindividualized treatment should be considered for Indonesian tuberculosis patients basedon genetics characteristics of patients.