Structure-activity relationship studies of 2-phenylbenzimidazoles and related organometallic complexes as antiplasmodial agents

Malaria remains a huge public health concern, affecting millions of people from all around the world. The widespread resistance by Plasmodium parasites to previously effective quinoline-based drugs and the emerging resistance to current antimalarial therapies, stresses the urgent need for the exploration and development of diverse new classes of compounds. Amongst other requirements, these diverse new compound classes should target resistant strains in particular. In this regard, benzimidazoles have been identified as promising potential drug candidates, displaying potent antiplasmodial activity. Furthermore, benzimidazoles can be chemically transformed into metal-containing organometallic complexes that elevate generally flat benzimidazoles to the third dimension. To date, examples of metal-containing benzimidazoles are extremely limited, with only two reported as having antiplasmodial activity. Thus, we report the syntheses of a series of substituted 2-phenylbenzimidazole ligands, from the cyclo-condensation of o-phenylenediamines and benzaldehyde, as well as the synthesis of Ru(II) and Ir(III) cyclometallated benzimidazole complexes. All of the compounds synthesised were fully characterised by 1H and 13C{1H} Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and Mass Spectrometry. The synthesised 2-phenylbenzimidazoles and metal complexes were screened in vitro against the chloroquine-sensitive NF54 strain and selected complexes were screened against the chloroquine-resistant K1 strain of P. falciparum. In addition, selected compounds were also tested against the Chinese Hamster Ovarian (CHO) mammalian cell-line to evaluate their selectivity. The 2-phenylbenzimidazoles generally displayed weak to moderate antiplasmodial activity against the chloroquine-sensitive NF54 strain, where IC50 values ranged from 3.27 – 32.97 µM. Furthermore, it was demonstrated that the antiplasmodial activities of the 2-phenylbenzimidazoles increased significantly upon metal complexation, using Ru and Ir metals. In general, the antiplasmodial activity of the Ru(II) complexes were significantly better compared to the Ir(III) complexes. The cyclometallated benzimidazole complexes were much more active across both parasite strains (0.12 < IC50 < 4.31), compared to the corresponding ligands tested. The unsubstituted Ru(II) and Ir(III) cyclometallated benzimidazole complexes were found to possess the most potent antiplasmodial activity against the NF54 strain, displaying IC50 values of 0.12 and 0.19 µM, respectively. In most cases, the resistance indices obtained for the select compounds tested were significantly lower compared to chloroquine, which suggested that the compounds are not cross-resistant with chloroquine. Furthermore, cytotoxicity studies indicated that the synthesised compounds had low cytotoxicity and were selective towards the malaria parasites. Additional studies which involved testing the aqueous solubility of selected compounds in PBS buffer at pH 6.5 showed that the introduction of water-solubilising groups improved the compounds solubility significantly. Preliminary mechanistic studies suggested that the synthesised benzimidazoles may have a different mode of action to chloroquine as the compounds did not inhibit β-haematin formation at the maximum concentration of 500 µM

PROMOTING STUDENTS’ READING FLUENCY AND MOTIVATION THROUGH SHARED-READING WITH ANIMATED-VIDEO STORY

This research was conducted to investigate whether there was a significant difference in achievement between students who were taught by using Shared Reading with Animated Video Story and those who were not taught by using Shared Reading with Animated Video Story in reading fluency in terms of accurate reading, reading speed and reading expression, and the motivation toward the use of Shared Reading with Animated Video Story in reading fluency. This research was an experimental research. The population of the research comprised 129 students; samples of the research were 41 students from population by using  random sampling, 21 students in class 7C as experimental group, and 20 students in the class 7F as control group. The instruments used to collect the data were test and questionnaire. The data obtained from both instruments were analyzed by using SPSS 23 The post-test result of the experimental group showed that ttest (2.680) was higher than ttable (1.67). Further, utilizing independent samples t test, the sig. 2-tailed value (0,004) (0.05) confirmed that Ha was accepted and H0 was rejected. Moreover, the students had a quite positive responses (85%) toward the use of Shared Reading With Animated Video Story. To sum up, the implementation of shared reading strategy with animated video story is effective in improving students’ reading fluency and motivation. It is recommended that future related research should be conducted in more diverse educational settings to see how shared reading with animated video story is implemented

IMPLEMENTASI BATAS WAKTU PENYELESAIAN PERKARA KORUPSI DI PENGADILAN TINDAK PIDANA KORUPSI TINGKAT PERTAMA DIHUBUNGKAN DENGAN MASA PENAHANAN HAKIM DI PENGADILAN TINGKAT PERTAMA

Kasus korupsi merupakan salah satu kejahatan yang dikategorikan sebagai kejahatan luar biasa yang memerlukan cara khusus dalam penyelesaiannya. Oleh karena itu, pada tahun 2009, pemerintah Indonesia meresmikan undang-undang yang dibentuk khusus untuk membantu penegakan hukum bagi tindak pidana korupsi di tingkat Pengadilan yang diberi nama Undang-Undang Nomor 46 Tahun 2009 tentang Pengadilan Tindak Pidana Korupsi. Salah satu bentuk kekhususan penyelesaian perkara korupsi berdasarkan undang-undang ini adalah terdapatnya batas waktu untuk menyelesaikan perkara korupsi di berbagai tingkat. Seperti misalnya, pada Pasal 26 Undang-Undang Nomor 46 Tahun 2009 tentang Pengadilan Tindak Pidana Korupsi yang berisikan tentang batas waktu penyelesaian perkara korupsi di tingkat pertama yakni di tingkat Pengadilan Negeri. Berdasarkan hal diatas, identifikasi masalah adalah bagaimana implementasi batas waktu penyelesaian tindak pidana korupsi di tingkat pertama di Pengadilan Negeri Bandung dihubungkan dengan masa penahanan hakim? Apa yang menjadi hambatan penegak hukum khususnya hakim Pengadilan Negeri Bandung untuk menyelesaikan perkara tindak pidana korupsi sesuai dengan batas waktu yang ditentukan oleh undang-undang? Upaya apa yang dapat dilakukan aparat penegak hukum khususnya hakim Pengadilan Negeri Bandung untuk menyelesaikan kasus tindak pidana korupsi sesuai dengan batas waktu yang ditentukan undang-undang? Dalam menganalisis hasil penelitian, peneliti menggunakan metode penelitian dengan spesifikasi penelitian menggunakan deskriptif analitis yaitu menganalisis permasalahan yang ada melalui data yang telah dikumpulkan kemudian diolah serta disusun dengan berlandasakan kepada teori-teori dan konsep-konsep yang digunakan. Metode pendekatan yang digunakan dalam penelitian ini adalah yuridis normatif yaitu pendekatan atau penelitian hukum dengan menggunakan metode pendekatan/teori/konsep dan metode analisis yang termasuk dalam disiplin Ilmu Hukum yang dogmatis. Metode analisis data yang digunakan adalah yuridis kualitatif yaitu analisis dengan penguraian deskriptif analitis dan preskriptif (bagaimana seharusnya) dengan tidak menggunakan data statistik dan rumus matematik. Kesimpulan dalam penelitian ini adalah implementasi Pasal 26 Undang-Undang Nomor 46 Tahun 2009 Tentang Pengadilan Tindak Pidana Korupsi masih belum diterapkan sebagaimana mestinya dalam beberapa kasus khususnya di Pengadilan Negeri Bandung sedangkan untuk masa penahanan hakim dalam kedua kasus tersebut masih terpenuhi. Hal ini disebabkan adanya pengaruh dari beberapa hambatan seperti bertepatan dengan hari libur nasional, banyaknya saksi dan alat bukti yang terlibat dan alasan tidak terduga seperti sakit dan keterlambatan kehadiran para pihak. Hambatan-hambatan seperti ini dapat diminimalkan dengan beberapa upaya seperti memaksimalkan persidangan yang sedang berlangsung dan memaksimalkan hari kerja. Kata kunci : Batas Waktu, Tindak Pidana Korupsi, Peradilan tingkat pertama

Public Health and Drug Policing in Malaysia : Using Empirical Evidence for Advocacy

After declaring a “War on Drugs” in 2003, Malaysia adopted harm reduction as official policy in 2006 to reduce substance use related risks and subsequently implemented needle-and-syringe exchange programs and methadone maintenance therapies. Seven years after the inception of Malaysia’s harm reduction policy, the Centre of Excellence and Research in AIDS (CERiA) and the Malaysian AIDS Council (MAC) carried out qualitative research with police officers and people who use drugs to determine attitudes towards harm reduction and drug use, and to elicit perspectives on better approaches in drug law enforcement. We conducted qualitative research with 20 people who use drugs and 11 police officers based in police stations in various states in Malaysia (Kuala Lumpur, Pahang, and Kelantan). These interviews showed that police often lack understanding on the efficacy and operation of harm reduction programs. Interviews with people who use drugs pointed to a host of police practices that constitute barriers to treatment, including physical violence and psychological abuse, corrupt practices and failure to inform individuals of their rights. These results will inform subsequent quantitative surveys to generate further evidence on drug law enforcement and public health implications in Malaysia. Based on these empirical findings, we undertook evidence-based advocacy, maintaining an advocacy log containing key events including meetings with key officials, tweets, emails and text messages that contributed to improving police awareness about harm reduction and drug evidence-based drug policy. This chapter summarizes our approach to and results of evidence-informed advocacy work. Our experience of this qualitative research and its gains for advocacy demonstrate that larger scale interventions involving high-level police officials may be necessary to change policing practices, some of which are structural or are ingrained in police culture but oppose public health evidence. Numerous studies and reports have proven that harsh penalties and oppressive policing negatively impact public health, increase marginalisation, and increase drug-related crime, and that the inverse i.e. decriminalisation paired with access to voluntary health services improve public health and reduce drug-related crime. (Hughes & Stevens, 2012; Fullerton, et al, 2014; GCDP, 2014; Rhodes, et al, 2006) Negative practices have the potential to seep (and in some cases, are already seeping) into other agencies in drug policy and drug control. A consolidated written drug policy would assist in mitigating these issues, as we outline below.Non UBCUnreviewedFacultyGraduateUnknow

Quality A shared commitment; TqualityassuranceinbuildingTquality assurance in buildingT and construction

SIGLEAvailable from British Library Document Supply Centre- DSC:90/07872(Quality) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Pharmaceutical manufacturing (processing and packaging)

Available from British Library Document Supply Centre- DSC:91/18142(Pharmaceutical) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Quality Assurance for the Offshore Industry 1986

SIGLEAvailable from British Library Document Supply Centre- DSC:7168.13948(1986) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles

Benzimidazoles, such as albendazole, thiabendazole and omeprazole have antiplasmodial activity against Plasmodium falciparum and are widely used as scaffolds for metal-based drug research. Incorporating substituents with various lipophilic and electronic properties can influence trans-membrane interactions and concomitantly improve the biological activity. To study structure-activity relationships, a series of 2-phenylbenzimidazoles and their corresponding Ru(II), Ir(III) and Rh(III) cyclometallated complexes were synthesised and evaluated for antiplasmodial activity against the chloroquine-sensitive (NF54) strain of the human malaria parasite Plasmodium falciparum. Selected metal complexes were further screened against the multidrug-resistant (K1) strain. In general, the 2-phenylbenzimidazole ligands showed weak antiplasmodial activities (IC50 ∼ 17.66–22.32 μM) while an enhancement of antiplasmodial activity was observed upon coordination of the ligands with either ruthenium, iridium or rhodium. The new cyclometallated complexes were found to be active against both parasite strains, with IC50 values in the low to submicromolar range (0.12–5.17 μM). In addition, the metal complexes have relatively low cytotoxicity against mammalian Chinese Hamster Ovarian (CHO) cells