Pusat Penyelidikan Dadah dan Ubat-Ubatan - Tesis
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- PublicationDiscovery Of New Potential Pyrido[2,3-D]Pyrimidin-7-One Based Cdk4 Inhibitors Using Molecular Modelling Approaches(2023-02)Al Attraqchi, Omar Husham AhmedCyclin-dependent kinases (CDKs) are a class of regulatory enzymes that modulate various biochemical properties of the cell such as cell division. Different CDK enzymes have been shown to be promising biological targets for combating different types of cancer. In particular, the CDK4 enzyme has been observed to be overexpressed in several types of cancer including breast cancer. The usage of small-drug molecules that inhibits the activity of the CDK4 enzyme has proved to be clinically valid approach. However, currently available solutions suffer from various limitations such as insufficient activity. Among the most notable inhibitors of the CDK4 enzyme are the compounds based on the pyrido[2,3-d]pyrimidin-7-one scaffold. In this study, computer-aided drug design (CADD) methods including ligand-based and structure-based methods have been applied on the compounds derived from this scaffold. The applied CADD methods revealed the correlation of the physicochemical properties with the activity and gave insights into the binding process. The used ligand-based CADD methods included quantitative structure-activity relationship (QSAR) and pharmacophore modeling.
- PublicationModulation Of Dopaminergic System By Mitragynine And The Underlying Mechanisms Instigating Impairment Of Hippocampal Synaptic Plasticity(2023-09)Salim, Mohamad Azmeer Effendy MdMitragynine is the primary indole alkaloid of kratom (M. speciosa) Korth and is thought to be part of kratom’s main psychoactive components. Besides contributing to the addiction, it is known to induce rewarding effects by acting as an agonist to opioid receptors and block the dopamine D2 receptor. Moreover, mitragynine causes cognitive deficit and impairs the hippocampal synaptic plasticity, but the underlying mechanisms are still unknown. In the early part of the study, the modulation of dopaminergic system by mitragynine was investigated in rats treated with mitragynine (1 and 30 mg/kg) acutely (1-day treatment) and repeatedly (4-days treatment) through electroencephalography (EEG) recording. Level of dopamine release was quantified using electrochemical biosensor and ELISA kit analysis. The expression of dopamine transporter was measured using RT-qPCR. Results indicated that administration of mitragynine at both doses triggered changes in spectral frequencies demonstrating adaptations of dopaminergic system in freely moving rats. Repeated exposure of mitragynine (1 and 30 mg/kg) evoked increase of dopamine release after 4 days of administration, where at low dose (1 mg/kg) shows irregular increase of mitragynine released. High dose (30 mg/kg) shows a stable intensification of dopamine released, not after acute exposure in real time recording through an electrochemical biosensor. The adaptations of dopaminergic systems by mitragynine are coupled with increased expression of dopamine transporter in the prefrontal cortex.
- PublicationA Study On Drug Use And Criminal Behaviours Of Criminal Offenders In The State Of Penang(2023-01)Hadep Singh, Balber SinghPeople who use drugs (PWUDs) tend to commit crime under the influence of drugs compare with people without drug use history. Though researchers have argued that drug use can cause people to engage in crime, however, the relationship between drug use and crime seems insufficiently investigated. This study aims to investigate the criminal profile of Police detainees who were caught under the Penal Code (Act 574) for various crime offenses between June and December 2019 in the Northeast and Southwest Districts of Penang State. A total of 73 Police detainees were recruited through convenience sampling for this cross-sectional study. Majority were males (93%, n=68/73), most Malays (58%, n=42/73), and the sample’s mean age in this study was 32.8 years (SD=8.13). About 16% (n=12/73) of the detainees had previous drug rehabilitation history, while 55% (n=40/73) had been incarcerated before. Fifty-six percent (n=41/73) of the detainees were detained for non-violent offenses (e.g., property crime), and 44% for violent offenses (e.g., gang robbery, physical assault, etc.) under the Penal Code (Act 574). Of this, 81% (n=59/73) of the offenses were categorised as bailable offenses. As for their drug use status, 62% (n=45/73) of the detainees tested positive for illicit drug use, most (53%) for amphetamine-type stimulant (ATS) and opiate (18%), when they were brought into detention. Sixty-eight percent (n=50/73) of the detainees had illicit drug use history. Most (59%, n=43/73) reported committing crime individually, and 41% usually committed crime with their acquaintances. About 8% held dangerous weapons while committing crime, and 41% (n=30/73) claimed that they were ordered by their superiors to commit crime.
- PublicationA Study On Drug Use And Criminal Behaviours Of Criminal Offenders In The State Of Penang(2023-01)Hadep Singh, Balber SinghPeople who use drugs (PWUDs) tend to commit crime under the influence of drugs compare with people without drug use history. Though researchers have argued that drug use can cause people to engage in crime, however, the relationship between drug use and crime seems insufficiently investigated. This study aims to investigate the criminal profile of Police detainees who were caught under the Penal Code (Act 574) for various crime offenses between June and December 2019 in the Northeast and Southwest Districts of Penang State. A total of 73 Police detainees were recruited through convenience sampling for this cross-sectional study. Majority were males (93%, n=68/73), most Malays (58%, n=42/73), and the sample’s mean age in this study was 32.8 years (SD=8.13). About 16% (n=12/73) of the detainees had previous drug rehabilitation history, while 55% (n=40/73) had been incarcerated before. Fifty-six percent (n=41/73) of the detainees were detained for non-violent offenses (e.g., property crime), and 44% for violent offenses (e.g., gang robbery, physical assault, etc.) under the Penal Code (Act 574). Of this, 81% (n=59/73) of the offenses were categorised as bailable offenses. As for their drug use status, 62% (n=45/73) of the detainees tested positive for illicit drug use, most (53%) for amphetamine-type stimulant (ATS) and opiate (18%), when they were brought into detention. Sixty-eight percent (n=50/73) of the detainees had illicit drug use history. Most (59%, n=43/73) reported committing crime individually, and 41% usually committed crime with their acquaintances. About 8% held dangerous weapons while committing crime, and 41% (n=30/73) claimed that they were ordered by their superiors to commit crime.
- PublicationKetum (Mitragyna Speciosa Korth.) Consumption, Lipid Profile And Electrocardiogram (Ecg) Abnormalities(2023-07)Korindasamy, Novline YuvashneeKetum (Mitragyna speciosa Korth.) a native medicinal plant of Southeast Asia, has been used in Malaysia for decades for its unique curative properties. Given its broad therapeutic properties and increasing utility, ketum’s long-term safety profile, especially on its cardiotoxicity risk remains poorly investigated in regular ketum users. Given this research limitation, this study aims to evaluate the electrocardiogram (ECG) abnormalities and lipid profile between regular ketum users and healthy control subjects. A total of 200 respondents (n=100 regular ketum users and n=100 healthy control subjects) were recruited through convenience sampling from the northern peninsular state of Penang for this clinical, cross-sectional study. All were required to undergo an ECG evaluation, and blood samples were also drawn to characterize the respondent’s lipid profile. All males, a majority were Malays (97%, n=194/200), and the samples mean age in this study was 33 years (SD=6.7), while ketum users mean duration of ketum use was 6.4 years (SD=4.31). Ketum users mean systolic and diastolic blood pressure rates were 132.9 beats per minute (SD=17.3) and 77.1 beats per minute (SD=11.1), respectively.