Synthesis, bioactivity evaluation and computational studies of bisindolylmethane and flavone derivatives / Syahrul Imran Abu Bakar

Bisindolylmethane and flavone are well-known natural product scaffolds having important pharmacophores and they have gained tremendous interest owing to their remarkable potency and activity profile towards various target diseases. In this study novel bisindolylmethanes and flavones were synthesized to identify potential inhibitors for bacterial infection, cancer, and diabetes. One hundred twenty-nine (129) bisindolylmethane derivatives (Schiff base, thiourea, sulfonamide, and hydrazone) and 43 flavone derivatives (hydrazone and ether) were synthesized, evaluated for various in vitro bioactivities, and analyzed through computational studies to identify possible inhibition mechanisms. Antibacterial activity of bisindolylmethane Schiff bases showed that most compounds moderately inhibit Salmonella typhi, S. paratyphi A and S. paratyphi B bacterial strains. The results also reveals that compounds having halides and nitro substituents showed best antibacterial activity. Bisindolylmethane thioureas and sulfonamides were tested for carbonic anhydrase II inhibition activity. Molecular docking results suggest that nitro substituent at para position interacts well with Zn2+ ion and interferes with the Zn-OH-Thr199-Glu106 hydrogen bond network. Bisindole hydrazone in this study were synthesized through a three-step reaction. β-Glucuronidase inhibitory property of some derivatives were found to be very potent (0.1-83.5 μM). Docking studies showed that active compounds should have two or more hydroxyl groups substituted on carbon adjacent to each other for good interactions to take place

An Analysis of Psychological Trauma and Depression of Survivors in Recurring Disaster

The study aimed to determine psychological trauma and depression in survivors of recurring disasters (the 2004 and 2012 earthquakes in Aceh). A quantitative approach was used as the research design, 2 villages located in Banda Aceh were taken as the samples involving 60 respondents from the two villages. The respondents' criteria were: 1) experiencing two earthquakes in 2004 and 2012, 2) aged over 30 years. Data collection used a modification of the Hamilton Anxiety Rating Scale questionnaire, depression scale, and demographic data. The results showed that there was no correlation between psychological trauma and depression in survivors of the recurring earthquake in Aceh. Besides, based on the results of data analysis, there was a correlation between symptoms (p≤0,000), occupation (p≤0,030), and age (p≤0,015) with psychological trauma; and there was no correlation between potential disasters (p≤0,075), family support (p≤0,002), education (p≤0,181) coping ability (p≤0,401), the value of faith (p≤0,266), and income (p≤0,830) with psychological trauma. &nbsp

Synthesis, bioactivity evaluation and computational studies of bisindolylmethane and flavone derivatives / Syahrul Imran Abu Bakar

Bisindolylmethane and flavone are well-known natural product scaffolds having important pharmacophores and they have gained tremendous interest owing to their remarkable potency and activity profile towards various target diseases. In this study novel bisindolylmethanes and flavones were synthesized to identify potential inhibitors for bacterial infection, cancer, and diabetes. One hundred twenty-nine (129) bisindolylmethane derivatives (Schiff base, thiourea, sulfonamide, and hydrazone) and 43 flavone derivatives (hydrazone and ether) were synthesized, evaluated for various in vitro bioactivities, and analyzed through computational studies to identify possible inhibition mechanisms. Antibacterial activity of bisindolylmethane Schiff bases showed that most compounds moderately inhibit Salmonella typhi, S. paratyphi A and S. paratyphi B bacterial strains. The results also reveals that compounds having halides and nitro substituents showed best antibacterial activity. Bisindolylmethane thioureas and sulfonamides were tested for carbonic anhydrase II inhibition activity. Molecular docking results suggest that nitro substituent at para position interacts well with Zn2+ ion and interferes with the Zn-OH-Thr199-Glu106 hydrogen bond network. Bisindole hydrazone in this study were synthesized through a three-step reaction. β-Glucuronidase inhibitory property of some derivatives were found to be very potent (0.1-83.5 μM). Docking studies showed that active compounds should have two or more hydroxyl groups substituted on carbon adjacent to each other for good interactions to take place

Hubungan Kesiapsiagaan Dokter Pusat Kesehatan Masyarakat Kota Banda Aceh Dengan Motivasi Penanganan Pasien Kecelakaan Lalu Lintas

Tujuan penelitian ini adalah untuk mengetahui hubungan kesiapsiagaan dokter pusat kesehatan masyarakat kota Banda Aceh dengan motivasi penanganan pasien kecelakaan lalu lintas. Penelitian ini merupakan penelitian analitik observasional dengan desain cross sectional. Populasinya adalah seluruh dokter umum yang ada di Pusat Kesehatan Masyarakat wilayah Kota Banda Aceh, dengan jumlah sampel 30 orang. Hasil penelitian ini menunjukkan, tingkat kesiapsiagaan dokter berdasarkan parameter pengetahuan berada pada kategori sangat siap dengan 56,7% responden, tingkat kesiapsiagaan dokter berdasarkan parameter sikap dengan 91,2% responden termasuk dalam kategori sangat siap, tingkat kesiapsiagaan dokter diukur berdasarkan parameter rencana tanggap darurat sebanyak 66,7% responden termasuk dalam kategori sangat siap, tingkat kesiapsiagaan dokter berdasarkan parameter sumber daya mendukung sebanyak 63,3% responden termasuk dalam kategori sangat siap dan 93,3% responden memilki motivasi kuat dan hubungan kesiapsiagaan dengan motivasi penanganan pasien kecelakaan lalu lintas menunjukkan hubungan yang sedang dan berpola positif (p <0,001).(JKS 2016; 3: 153- 160

Evaluasi Partisipasi Pendidikan Kebencanaan Pada Mahasiswa Fakultas Kedokteran Universitas Syiah Kuala (Setelah Mengikuti Blok Disaster Management)

Indonesia kerap menghadapi berbagai macam bencana yang datang silih berganti. Gempa bumi, tsunami, banjir, longsor, gunung meletus dan angin puting beliung kerap terjadi di Indonesia. Hal ini disebabkan oleh kondisi geografis Indonesia khususnya Aceh yang sangat rawan bencana. Potensi bencana di Aceh sangat besar karena kondisi geografis, geologis, hidrologis, dan demografis yang sangat berperan dalam terjadinya bencana. Dokter merupakan profesi yang sangat dibutuhkan apabila terjadi bencana. Blok Disaster Management merupakan suatu blok dalam kurikulum pendidikan kedokteran yang membahas mengenai dasar-dasar bencana. Tujuan penelitian ini adalah untuk mengevaluasi dan menganalisis partisipasi mahasiswa Fakultas Kedokteran Universitas Syiah Kuala yang telah mengikuti blok Disaster Management angkatan 2009-2011. Penelitian kuantitatif dengan 238 subjek yang ditentukan dengan metode acak bertingkat ikut serta dalam penelitian ini. Data diperoleh melalui pengisian kuesioner sebanyak 10 pernyataan mengenai partisipasi disaster management. (JKS 2016; 3: 146- 152

Evaluation of a Series of 9,10-Anthraquinones as Antiplasmodial Agents

Background: A phytochemical study on medicinal plants used for the treatment of fever and malaria in Africa yielded metabolites with potential antiplasmodial activity, many of which are Anthraquinones (AQ). AQs have similar sub-structure as naphthoquinones and xanthones, which were previously reported as novel antiplasmodial agents. Objective: The present study aimed to investigate the structural requirements of 9,10- anthraquinones with hydroxy, methoxy and methyl substituents to exert strong antiplasmodial activity and to investigate their possible mode of action. Methods: Thirty-one AQs were synthesized through Friedel-Crafts reaction and assayed for antiplasmodial activity in vitro against Plasmodium falciparum (3D7). The selected compounds were tested for toxicity and probed for their mode of action against β-hematin dimerization through HRP2 and lipid catalyses. The most active compounds were subjected to a docking study using AutoDock 4.2. Results: The active AQs have similar common structural characteristics. However, it is difficult to establish a structure-activity relationship as certain compounds are active despite the absence of the structural features exhibited by other active AQs. They have either ortho- or meta-arranged substituents and one free hydroxyl and/or carbonyl groups. When C-6 is substituted with a methyl group, the activity of AQs generally increased. 1,3-DihydroxyAQ (15) showed good antiplasmodial activity with an IC50 value of 1.08 µM, and when C-6 was substituted with a methyl group, 1,3- dihydroxy-6-methylAQ (24) showed stronger antiplasmodial activity with an IC50 value of 0.02 µM, with better selectivity index. Compounds 15 and 24 showed strong HRP2 activity and mild toxicity against hepatocyte cells. Molecular docking studies showed that the hydroxyl groups at the ortho (23) and meta (24) positions are able to form hydrogen bonds with heme, of 3.49 Å and 3.02 Å, respectively. Conclusion: The activity of 1,3-dihydroxy-6-methylAQ (24) could be due to their inhibition against the free heme dimerization by inhibiting the HRP2 protein. It was further observed that the anthraquinone moiety of compound 24 bind in parallel to the heme ring through hydrophobic interactions, thus preventing crystallization of heme into hemozoin

Virtual screening-based identification of Potent DENV-3 RdRp protease inhibitors via in-house usnic acid derivative database

Dengue virus (DENV) is the causative agent of dengue fever, dengue hemorrhagic disease and dengue shock syndrome (DSS), transmitted predominantly in tropical and subtropical regions by Aedes aegypti. It infects millions of people and causes thousands of deaths each year, but there is no antiviral drug against DENV. Usnic acid lately piqued the interest of researchers for extraordinary biological characteristics, including antiviral activity. Based on high larvicidal activities against Aedes aegypti, this study aims to search usnic acid derivatives as novel anti-DENV agents through a combination of ligand-based and pharmacophore-based virtual screening. One hundred and sixteen (116) usnic acid derivatives were obtained from a database of 428 in-house usnic acid derivatives through pharmacophore filtering steps. Subsequent docking simulation on DENV-3 NS-5 RdRp afforded 41 compounds with a strong binding affinity towards the enzyme. The pharmacokinetics and drug likeness prediction resulted in seven hit compounds, which eventually undergo cytochrome P450 enzyme screening to obtain the lead compound, labelled as 362. In addition, molecular dynamic (MD) simulation of lead compound 362 was performed to verify the stability of the docked complex and the binding posture acquired in docking experiments. Overall, the lead compounds have shown a high fit value of pharmacophore, strong binding affinity towards RdRp enzyme, good pharmacokinetics, and drug likeness properties. The discovery of a new usnic acid derivative as a novel anti-DENV agent targeting RdRp could lead to further drug development and optimization to treat dengue

Usnic acid as potential inhibitors of BCL2 and P13K protein through network pharmacology-based analysis, molecular docking and molecular dynamic simulation

Usnic acid (UA) lately piqued the interest of researchers for its extraordinary biological characteristics, including anticancer activity. Here, the mechanism was clarified through network pharmacology,molecular docking and molecular dynamic simulation. Sixteen proteins were selected through network pharmacology study as they are probable to interact with UA. Out of these proteins, 13 were filtered from PPI network analysis based on their significance of interactions (p < 0.05). KEGG pathway analysis has also aided us in determining the three most significant protein targets for UA, which are BCL2, PI3KCA and PI3KCG. Therefore molecular docking and molecular dynamic (MD) simulations throughout 100 ns were performed for usnic acid onto the three proteins mentioned. However, UA's docking score in all proteins is lower than their co-crystalised ligand, especially for BCL2 (−36.5158 kcal/mol) and PI3KCA (−44.5995 kcal/mol) proteins. The only exception is PI3KCG which has comparable results with the co-crystallised ligand with (−41.9351 kcal/mol). Furthermore, MD simulation has also revealed that usnic acid does not stay fit in the protein throughout the simulation trajectory for PI3KCA protein evident from RMSF and RMSD plots. Nevertheless, it still poses good ability in inhibiting BCL2 and PI3KCG protein in MD simulation. In the end, usnic acid has exhibited good potential in the inhibition of PI3KCG proteins, rather than the other proteins mentioned. Thus further study on structural modification of usnic acid could enhance the ability of usnic acid in the inhibition of PI3KCG as anti-colorectal and anti-small cell lung cancer drug candidate

Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of b-Glucuronidase and in silico study

New benzimidazole analogues (1–18) were synthesized and characterized through differ- ent spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for b-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 – 0.10 to 39.60 – 0.70 lM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 lM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 – 0.10, 1.70 – 0.10, 2.30 – 0.10, 5.30 – 0.20, 6.20 – 0.20 and 8.10 – 0. 20 lM respectively, showed excellent b-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to stan- dard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from into vitro assay. The molecular docking results clearly highlighted how sub- stituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced b-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic

Virtual screening of bioactive anti-SARS-CoV natural products and identification of 3β,12-diacetoxyabieta-6,8,11,13-tetraene as a potential inhibitor of SARS-CoV-2 virus and its infection related pathways by MD simulation and network pharmacology

Since the first prevalence of COVID-19 in 2019, it still remains the most devastating pandemic throughout the world. The current research aimed to find potential natural products to inhibit the novel coronavirus and associated infection by MD simulation and network pharmacology approach. Molecular docking was performed for 39 natural products having potent anti-SARS-CoV activity. Five natural products showed high binding interaction with the viral main protease for the SARS-CoV-2 virus, where 3β,12-diacetoxyabieta-6,8,11,13 tetraene showed stable binding in MD simulation until 100 ns. Both 3β,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A targeted 11 common genes that are related to COVID-19 and interact with each other. Gene ontology development analysis further showed that all these 11 genes are attached to various biological processes. The KEGG pathway analysis also showed that the proteins that are targeted by 3β,12-diacetoxyabieta-6,8,11,13 tetraene and tomentin A are associated with multiple pathways related to COVID-19 infection. Furthermore, the ADMET and MDS studies reveals 3β,12-diacetoxyabieta-6,8,11,13 as the best-suited compound for oral drug delivery