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  1. Ramli AH, Mohd Faudzi SM
    Arch Pharm (Weinheim), 2023 Dec;356(12):e2300391.
    PMID: 37806761 DOI: 10.1002/ardp.202300391
    Asia is a hotspot for infectious diseases, including malaria, dengue fever, tuberculosis, and the pandemic COVID-19. Emerging infectious diseases have taken a heavy toll on public health and the economy and have been recognized as a major cause of morbidity and mortality, particularly in Southeast Asia. Infectious disease control is a major challenge, but many surveillance systems and control strategies have been developed and implemented. These include vector control, combination therapies, vaccine development, and the development of new anti-infectives. Numerous newly discovered agents with pharmacological anti-infective potential are being actively and extensively studied for their bioactivity, toxicity, selectivity, and mode of action, but many molecules lose their efficacy over time due to resistance developments. These facts justify the great importance of the search for new, effective, and safe anti-infectives. Diarylpentanoids, a curcumin derivative, have been developed as an alternative with better bioavailability and metabolism as a therapeutic agent. In this review, the mechanisms of action and potential targets of antimalarial drugs as well as the classes of antimalarial drugs are presented. The bioactivity of diarylpentanoids as a potential scaffold for a new class of anti-infectives and their structure-activity relationships are also discussed in detail.
  2. Rezaei AR, Ismail Z, Niksokhan MH, Dayarian MA, Ramli AH, Yusoff S
    Environ Monit Assess, 2021 Mar 31;193(4):241.
    PMID: 33791871 DOI: 10.1007/s10661-021-09010-4
    Stormwater runoff is a major concern in urban areas which is mostly the result of vast urbanization. To reduce urban stormwater runoff and improve water quality, low impact development (LID) is used in urban areas. Therefore, it is vital to find the optimal combination of LID controls to achieve maximum reduction in both stormwater runoff and pollutants with optimal cost. In this study, a simulation-optimization model was developed by linking the EPA Storm Water Management Model (SWMM) to the Multi-Objective Particle Swarm Optimization (MOPSO) using MATLAB. The coupled model could carry out multi-objective optimization (MOO) and find potential solutions to the optimization objectives using the SWMM simulation model outputs. The SWMM model was developed using data from the BUNUS catchment in Kuala Lumpur, Malaysia. The total suspended solids (TSS) and total nitrogen (TN) were selected as pollutants to be used in the simulation model. Vegetated swale and rain garden were selected as LID controls for the study area. The LID controls were assigned to the model using the catchment characteristics. The target objectives were to minimize peak stormwater runoff, TSS, and TN with the minimum number of LID controls applications. The LID combination scenarios were also tested in SWMM to identify the best LID types and combination to achieve maximum reduction in both peak runoff and pollutants. This study found that the peak runoff, TSS, and TN were reduced by 13%, 38%, and 24%, respectively. The optimal number of LID controls that could be used at the BUNUS catchment area was also found to be 25.
  3. Wafa SW, Talib RA, Hamzaid NH, McColl JH, Rajikan R, Ng LO, et al.
    Int J Pediatr Obes, 2011 Jun;6(2-2):e62-9.
    PMID: 21604965 DOI: 10.3109/17477166.2011.566340
    CONTEXT: Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world.
    AIM: To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia.
    METHODS: Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days).
    RESULTS: The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group.
    CONCLUSIONS: Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes.
  4. Mohd Fahmi MSA, Swain P, Ramli AH, Wan Ibrahim WN, Saleh Hodin NA, Abu Bakar N, et al.
    Heliyon, 2023 Feb;9(2):e13685.
    PMID: 36852036 DOI: 10.1016/j.heliyon.2023.e13685
    Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABAA, -8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action.
  5. Ramli AH, Swain P, Mohd Fahmi MSA, Abas F, Leong SW, Tejo BA, et al.
    Heliyon, 2024 Mar 15;10(5):e27462.
    PMID: 38495201 DOI: 10.1016/j.heliyon.2024.e27462
    Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC50 of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.
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