Jufrizal Syahri
@umri.ac.id
Department of Chemistry
Universitas Muhammadiyah Riau
EDUCATION
Doctor - Universitas Gadjah Mada
Master - Universitas Andalas
Bachelor - Universitas Riau
RESEARCH INTERESTS
Drug Discovery
Synthesis
Organic
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Jufrizal Syahri, Rahmiwati Hilma, Amatul Hamizah Ali, Norzila Ismail, Ng Yee Ling, Nurlaili, Beta Achromi Nurohmah, Hani Kartini Agustar, Lau Yee Ling, and Jalifah Latip
Royal Society of Chemistry (RSC)
Research on the antimalarial effect of aminoalkyl chalcone derivatives against Plasmodium falciparum and Plasmodium knowlesi has bolstered efforts in drug discovery to combat cases of drug resistance.
Jufrizal Syahri, Rahmiwati Hilma, Nurlaili, Helvina Saputri, Sri Zulfiza Nasution, and Beta Achromi Nurohmah
AIP Publishing
Jufrizal Syahri, Rahmiwati Hilma, Nurlaili Nurlaili, Meidita Kemala Sari, Neni Frimayanti, Amatul Hamizah Ali, and Jalifah Latip
Penerbit Universiti Kebangsaan Malaysia (UKM Press)
Multi-resistance cases with antimalarial drugs had been developed in over the years. One of the ways of developing antimalarial drugs is to focus on searching for the potential antifolate inhibitors against Plasmodium sp. from synthetic or natural products. The aims of this research was to synthesis secondary amine-substituted eugenol compounds through the Mannich reaction for antimalarial evaluation using Plasmodium falciparum 3D7. The compounds were also evaluated on Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) as a protein target and the compounds’ drug-likeness properties were determined. Five secondary amine-substituted eugenol compounds (1a-e) were synthesized via substitution of the secondary amine i.e., pyrrolidine, piperidine, methyl piperidine, and morpholine in the eugenol structures. The plasmodium lactate dehydrogenase assay (pLDH) showed that 1a and 1c had good antimalarial effects against P. falciparum 3D7 with the IC50s values of 0.89 mM and 0.62 mM, respectively. The molecular docking analysis showed that 1a and 1c had perfect interaction with PfDHFR-TS (PDB ID: 1J3I) with strong hydrogen bond interactions occurring with PfDHFR-TS protein. The eugenol derivatives 1a and 1c exerted CDOCKER binding energies of -6.1407 and -6.6536 kcal/mol, respectively. Based on this research, it was found that PfDHFR-TS is a plausible protein target for the synthesized secondary amine-substituted eugenol in P. falciparum infection. The substitution of a secondary amine group for eugenol significantly enhanced the antimalarial properties of the compounds. Thus, eugenol derivatives are potential compounds to be pursued to combat folate resistance in malarial infection.
Linda Ekawati Linda Ekawati, Beta Achromi Nurohmah Beta Achromi Nurohmah, Jufrizal Syahri Jufrizal Syahri, and Bambang Purwono Bambang Purwono
Penerbit Universiti Kebangsaan Malaysia (UKM Press)
The synthesis, in vitro antimalarial assay, molecular docking, drug-likeness analysis, and ADMET prediction of substituted 3-styryl-2-pyrazoline derivatives as antimalaria have been conducted. The synthesis of N-phenyl (1a‒3a) and N-acetyl-substituted (1b‒3b) 3-styryl-2-pyrazolines was carried out using dibenzalacetone derivatives and hydrazine hydrate or phenylhydrazine. An in vitro antimalarial assay was conducted against the chloroquine-sensitive Plasmodium falciparum 3D7 strain, while molecular docking was performed toward the crystal protein of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 1J3I). Furthermore, the prediction of drug-like properties was determined by assessing Lipinski’s rules, and the pharmacokinetic parameters were also studied in-silico, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). The in vitro assay showed that 3a (IC50 0.101 µM) has excellent antimalarial activity, followed by 2a (0.177 µM), and 1b (0.258 µM). Molecular docking has supported the in vitro assay by showing the lowest CDOCKER energy for 3a (‒56.316 kcal/mol), then 2a (‒51.2603 kcal/mol), and 1b (‒48.8774 kcal/mol). The drug-like properties showed that all of the prepared compounds were acceptable based on Lipinski’s rules and predicted to be potentially orally bioavailable. The ADMET analysis provided information that 3a and 2a could be proposed as the best lead antimalarial drugs with further modification to reduce the lipophilicity and toxicity properties.
Emmy Yuanita, Sudirman Sudirman, Ni Komang Tri Dharmayani, Maria Ulfa, Saprizal Hadisaputra, and Jufrizal Syahri
Universitas Jenderal Soedirman
Covid-19 has caused more than 14 million confirmed cases and more than 6 hundred deaths as of 21 July 2020 globally. However, there is no approved drug to treat the disease. Xanthone is a potential therapeutic option for the virus that have been tested using molecular docking. There were 12 of xanthone compounds and its derivatives which have been docked against two protein crystals, 2GX4.pdb and 6FV1.pdb, which obtained two potential compounds of hydroxyxanthone derivatives with sulfonate and chloro substitution. These compounds are potentially developed into one of the agents for the treatment of infection COVID-19 disease. Based on energy data and interactions with amino acid residues when compared with its own native ligands, namely NOL and E8E, respectively. Energy docking and energy docking interactions are equal to - 43.3057and - 45.5805 Kcal/mol respectively, during interactions with amino acid residues in the form of Gly 142, His 163, Cys144, Glu166, Gln164 and His 41. Based on these two data, it can be concluded that trihydroxyxanthone compounds 4 and 8 with chloro and sulfonate substitution are very potential to be developed as drug agents for Covid-19 disease therapy through protease inhibition.
Ika Septiana, Bambang Purwono, Chairil Anwar, Beta Achromi Nurohmah, and Jufrizal Syahri
Universitas Gadjah Mada
Series of 2-aryl-4,5-diphenyl-1H-imidazole derivatives of 2-(4-hydroxy-3-methoxyphenyl)-4,5-diphenyl-1H-imidazole (1), 2-(4,5-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (2) and 2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole (3) were produced and evaluated for their in vitro antimalarial activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. A molecular docking study was also carried out against the crystal protein of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 1J3I.pdb) to predict the interaction between the compounds and protein. The physicochemical and pharmacokinetic parameters were computationally performed to predict the parameters of the absorption, distribution, metabolism, excretion, and toxicity (ADMET). Imidazoles were synthesized from aryl aldehyde derivatives with benzyl and ammonium acetate in glacial acetic acid using microwave-assisted-organic synthesis. Compounds 1, 2, and 3 were produced in 64.33, 50.56, and 70.55% yields, respectively. The IC50 of compounds 1, 2, and 3 against chloroquine-sensitive Plasmodium falciparum 3D7 strain was found to be 1.14, 5.28, and 2.42 µM, respectively. The molecular docking study agreed with the in vitro data by showing the lowest CDOCKER energy for compound 1 (-47.48 kcal/mol), followed by 3 (-43.79 kcal/mol) and 2 (-41.47 kcal/mol). The physicochemical and pharmacokinetic parameters showed that imidazoles 1, 2, and 3 obeyed Lipinski rules of five to propose as lead compounds for the antimalarial agents.
Nurlaili, Helvina Saputri, Sri Zulfiza Nasution, Rahmiwati Hilma, and Jufrizal Syahri
AIP Publishing
Lalu Rudyat Telly SAVALAS, Asih LESTARİ, Munirah MUNİRAH, Suryawati FARİDA, Dedy SUHENDRA, Dina ASNAWATİ, Jannatin 'ARDHUHA, Baiq SARI NİNGSİH, and Jufrizal SYAHRİ
Journal of the Turkish Chemical Society, Section A: Chemistry
Emmy Yuanita, Sudirman, Ni Komang Tri Dharmayani, Maria Ulfa, and Jufrizal Syahri
Elsevier BV
Quantitative structure–activity relationship (QSAR) and molecular docking approach were carried out to design novel anti-tuberculosis agents based on xanthone derivatives. QSAR designed new compounds were calculated by Austin Model 1 (AM1) methods and analysis of multi-linear regression (MLR). The result showed that the best model as follows: Log IC50 = 3.113 + 11.627 qC1 + 15.955 qC4 + 11.702 qC9, this result has appropriate some statistical parameters (PRESS = 2.11, r2 = 0.730, SEE = 0. 3545, R = 0.6827, FCal/FTab = 4.68), and being used to design a potential anti-tuberculosis drugs with substituted amide, sulfoxide, and carboxylate group xanthone scaffold by a number of their inhibitory concentration (IC50). The mechanism action of sulfonamide substituted on the xanthone scaffold as anti-tuberculosis was carried out using molecular docking. Docking inhibition studies were carried out on MTB C171Q receptor (4C6X.pdb) as KasA inhibitors using by the discovery studio. Based on the binding interaction showed, the sulfonamide substituted xanthone has potential being the anti-tuberculosis drugs by KasA inhibitor for target drug activity.
Jufrizal Syahri, Hasmalina Nasution, Beta Achromi Nurohmah, Bambang Purwono, Emmy Yuanita, Nur Hanis Zakaria, and Nurul Izzaty Hassan
Penerbit Universiti Kebangsaan Malaysia (UKM Press)
E. Yuanita, I. M. Sudarma, N. M. Sudewiningsih, J. Syahri, N. K. T. Dharmayani, Sudirman, M. Ulfa, and I. Sumarlan
AIP Publishing
Antibacterial assay of series hydroxyxanthone that was a synthesis via cyclization of phenol derivatives and acid derivatives with Eaton Reagent has been investigated through Escherichia coli, Bacillus cereus, Staphylococcus aureus and Salmonella typhimurium by diffusion well method. The possess antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) has been reported by molecular docking. The result reveals that the 1,3,6-tryhydroxyxanthone were effective in inhibiting the growth of Escherichia coli, Bacillus cereus, Staphylococcus aureus and Salmonella typhimurium in the inhibition zone of 30, 30, 35, than 34 mm respectively with MIC at 10%. There was a binding interaction between 1,3,6-tryhydroxyxanthone and the amino acid residues such as His38, His35, Val177, Lys150 and Met41 into methicillin-resistant Staphylococcus aureus (MRSA) (2x3f.pdb).
J. Syahri, Suwantono, H. Nasution, B. A. Nurohmah, and Emmy Yuanita
AIP Publishing
Resistance to antibacterial drugs is a problem in the global public health that must be conquered immediately by finding new antibacterial drugs. This study has been carried out to rationally design fluoroquinolone derivative compounds as antibacterial using QSAR method. The basis set used for molecular optimization was semiempirical Austin Model 1 (AM1) and the statistical analysis used was multilinear regression (MLR). The best QSAR equation model obtained was Log MIC50 = 473.758 – 92.342 (qC9) + 461.068 (qO11) + 192.743 (qC16) – 277.851 (qC20) + 1004.598 (LUMO).
Jufrizal Syahri, Hasmalina Nasution, Beta Achromi Nurohmah, B. Purwono and E. Yuanita
Journal of Applied Pharmaceutical Science
Three chalcone derivatives with amine groups (4a–c) were synthesized and evaluated for their antimalarial activity. Three aminoalkylated chalcone derivatives (4a–c) have been prepared through Claisen–Schmidt condensation reaction from vanillin and chloroacetophenone, followed by the Mannich reaction to add amine group. The structure of the compounds was confirmed by the spectrophotometric analysis using mass spectrometers (MS) and proton and carbon nuclear magnetic resonance (1Hand 13C-NMR) spectroscopy. Antimalarial activity of 4a–c was evaluated against Plasmodium falciparum (3D7) strain, and the molecular docking of 4b was performed to understand the interaction against Pf DHFR-TS protein (1J3I.pdb). The prepared aminoalkylated chalcone (4a–c) was obtained in a yield of 80%, 75%, and 70%. The addition of morpholine (4a), piperidine (4b), and diethylamine (4c) as amine groups significantly could improve the antimalarial activity with IC50 of 0.62, 0.54, and 1.12 μM, respectively (strong activity), compared with the chalcone without amine group (3) with IC50 of 25.84 μM (moderate activity). The molecular docking of compound 4b exhibited strong hydrogen bond interaction with ILE112, ILE64, SER111, SER108, ASP54, TYR170, and PRO113 residues with CDOCKER interaction energy of −48.84 kcal/mol. Thus, aminoalkylated chalcone could be proposed for further studies and developed into antimalarial drug candidates.
Jufrizal Syahri, Nurul Hidayah, Rahmiwati Hilma, Beta Achromi Nurohmah, and Emmy Yuanita
Universitas Jenderal Soedirman
This study aimed to propose new indole derivatives as anticancer through Quantitative Structure-Activity Relationship (QSAR) and molecular docking method. The best predicted anticancer activity of indole derivatives was recommended based on the QSAR equation. A data set consist of 18 indole derivatives from literature with anticancer activity against the A498 cell line was used to generate a QSAR model equation. The data set was divided randomly into training (14) and test (4) set compounds. The structure of indole compound was optimized first using AM1 semi-empirical methods, and the descriptors involved were analyzed using Multiple Linear Regression (MLR). The best QSAR equation obtained was Log IC50 = 65.596 (qC2) + 366.764 (qC6) – 92.742 (qC11) + 503.297 (HOMO) – 492.550 (LUMO) – 76.966. Based on the QSAR model, varying electron-withdrawing groups in C2 and C6 atom, as well as adding electron-donating groups in C11 were proposed could increase the anticancer activity of the indole derivatives. The QSAR analysis showed that compound 15 has the best predicted anticancer activity, supported by molecular docking results that showed hydrogen bond interaction with essential amino acids to build anticancer activity such as MET769, THR830, and THR766 residues.
Lalu Rudyat Telly Savalas, Baiq Repika Nurul Furqon, Dina Asnawati, Jannatin 'Ardhuha, Prapti Sedijani, Saprizal Hadisaputra, Baiq Nila Sari Ningsih, and Jufrizal Syahri
Polskie Towarzystwo Biochemiczne (Polish Biochemical Society)
Small protein tyrosine phosphatase (PtpA) of Mycobacterium tuberculosis is attributed to the development of latent tuberculosis infection, and hence bocomes an interesting target for drug development. In this communication, inhibition of PtpA by naturally occurring fatty acids cis-2 and trans-2-eicosenoic acid is investigated. Mtb PtpA was heterologously expressed in Escherichia coli, and the activity of PtpA was inhibited by cis-2 and trans-2 eicosenoic fatty acids. Both compunds showed strong inhibition of PtpA activity with IC50 at low micromolar concentration. As comparison, trans-11-eicosenoic acid only slightly inhibit PtpA. In silico analysis confirmed the inhibition of PtpB by cis-2-eicosenoic acid by formation of several hydrogen bonds. These findings show that cis-2 and trans-2 eicosenoic fatty acids are potential candidates for latent tuberculosis inhibitors.
Emmy Yuanita, Harno Dwi Pranowo, Mustofa Mustofa, Respati Tri Swasono, Jufrizal Syahri, and Jumina Jumina
Institute of Chemistry of Academy of Science of Moldova
Xanthone compounds are of great interest due to their wide range of biological applications. Xanthone compounds can be obtained by structural modification of the substituent on the xanthone rings through various reactions. In this study, the chloro-substituted hydroxyxanthones (4a-c) were prepared by cyclodehydration of acid derivatives and substituted phenol in the presence of Eaton reagent to afford 3a-c, followed by halogenation step to electrophilic substitution of chlorine in a moderate yield. The in vitro anticancer activity study on various cell lines showed that there was an enhanced activity of compounds 4a-c in comparison to 3a-c. It has been shown that compounds 4a-c have the best anticancer activity only toward P388 murine leukaemia cells with IC50 of 3.27, 1.809 and 0.18 μg/mL, respectively. The results revealed that the chloro functional group increases the anticancer activity of the hydroxyxanthone derivatives. As for the selectivity index, the number was increased from a range of 0.88-843 (3a-c) to 3.33-9199.67 (4a-c). This result indicates that the hydroxyxanthone derivatives (4a-c) have potential to be developed into chemotherapy agents due to their higher sensitivity and selectivity. Molecular docking studies showed that there was a binding interaction between 4c and the amino acid residues such as Asp810, Cys809, Ile789, His790, and Leu644 of protein tyrosine kinase receptor (PDB ID: 1T46).
Emmy Yuanita, , Harno Dwi Pranowo, Dwi Siswanta, Respati Tri Swasono, Mustofa Mustofa, Abdul Karim Zulkarnain, Jufrizal Syahri, Jumina Jumina, ,et al.
Lviv Polytechnic National University
За допомогою одностадійої реакції цикло-
дегідрування похідних гідроксибензенової кислоти (саліцилова
або резорцилова кислота) з флороглюціном або пірогалолом у
присутності реагенту Ітона (P2O5/MeSO3H) одержано нові
сполуки гідроксиксантону. Для визначення інгібуючої
концентрації (IC50) синтезованих сполук їх антиокиснювальну
активність перевірено за допомогою 2,2-дифеніл-1-пікрилгід-
разилу. Цитотоксичність отриманих сполук оцінено MТT-
тестом на лінії клітин Vero. Встановлено, що положення та
кількість гідроксильних груп можуть суттєво вплинути на
потенційну антиокиснювальну активність приготовлених
сполук. Показано, що синтезовані сполуки гідроксиксантону
можна класифікувати як сильні антиоксиданти та їх можна
використовувати в промисловості.
Jufrizal Syahri, Emmy Yuanita, Beta Achromi Nurohmah, Ria Armunanto, and Bambang Purwono
Medknow
Abstract Objective To investigate in vitro antimalarial activity of chalcone derivative compounds against Plasmodium falciparum 3D7 ( Pf 3D7) strain and in silico antimalarial activity. Methods Synthesis of the chalcone derivatives was conducted via Claisen-Schmidt method using NaOH 60% base as catalyst. An in vitro antimalarial activity assay was carried out according to the Rieckmann method against the chloroquine-sensitive Pf 3D7 strain. Molecular docking studies of the prepared compounds were performed using Discovery Studio 3.1 (Accelrys, Inc., San Diego, USA) software to dihydrofolate reductases–thymidylate synthase ( Pf DHFR-TS) protein with Protein Data Bank ID of 1J3I.pdb (sensitive-protein) and ID: 4DP3.pdb (resistance-protein). Results This work has successfully synthesized seven chalcone derivatives with a great antimalarial activity. It has been revealed that allyloxy, hydroxy and alkoxy functional groups could increase the antimalarial activity of the chalcone derivatives. The best antimalarial activity of the prepared compounds was possessed by 3b with an IC 50 value of 0.59 μM and categorized as an excellent antiplasmodial. Molecular docking studies of 3b showed binding interaction with the amino acid residues such as Ala16, Ile164, Phe58, Tyr170 of the 1J3I.pdb protein and also Ala16, Phe58, Ile112, Met55 of the 4DP3.pdb protein. Conclusions An in vitro antimalarial assay of the prepared chalcone derivative (3a–g) showed an excellent and good antiplasmodial activity against the chloroquine-sensitive Pf3D7 strain. In silico antimalarial studies revealed that 3a–g made binding interaction with both sensitive-protein (1J3I.pdb) and resistance-protein (4DP3.pdb), which means that they were both active against chloroquine-sensitive and resistant plasmodium strain.
Jufrizal Syahri, , Kamal Rullah, Ria Armunanto, Emmy Yuanita, Beta Achromi Nurohmah, Mohd Fadhlizil Fasihi Mohd Aluwi, Lam Kok Wai, Bambang Purwono, ,et al.
Asian Pacific Journal of Tropical Medicine Press
Jufrizal Syahri, Emmy Yuanita, Beta Achromi Nurohmah, Muhammad Hizbul Wathon, Rahmadini Syafri, Ria Armunanto, and Bambang Purwono
Oriental Scientific Publishing Company
The rational design of eighteen new antimalarial compounds from xanthone derivatives has been conducted based on Quantitative Structure-Activity Relationship (QSAR) calculation using semiempirical AM1 methods. The best equation model obtained from QSAR calculation was Log pIC50 = 2.997 29.256 (qO8) 138.234 (qC9) 6.882 (qC12) 107.836 (qC14) + 48.764 (qO15). Among the designed compounds, 3,6-dihydroxy-9H-xanthen-9-one (26) and 3,4,6-trihydroxy-9H-xanthen9-one (27) have been synthesized and investigated their in-vitro antimalarial activities against the chloroquine-sensitive 3D7 strain. An in-vitro antimalarial activity of compound 26 and 27 showed to be highly potential as antimalarial compounds with IC50 of 0.71 and 0.11 μM respectively. Molecular docking studies of compound 26 and 27 showed the formation of a binding interaction between the compounds with the amino acids Ala16, Ser108, Phe58, Asp54 and Leu46, which is the crucial amino acids for antimalarial activity based on the protein-ligand co-crystal structure of WR99210 (1,3,5-triazine, a pre-clinical molecule as P. falciparum DHFR-TS inhibitor).