Displaying publications 81 - 94 of 94 in total

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  1. Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin -induced diabetic albino wistar rats
    Taha M, Imran S, Salahuddin M, Iqbal N, Rahim F, Uddin N, et al.
    Bioorg Chem, 2021 05;110:104808.
    PMID: 33756236 DOI: 10.1016/j.bioorg.2021.104808
    We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.
  2. Fulltext Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning
    Cromwell EA, Osborne JCP, Unnasch TR, Basáñez MG, Gass KM, Barbre KA, et al.
    PLoS Negl Trop Dis, 2021 07;15(7):e0008824.
    PMID: 34319976 DOI: 10.1371/journal.pntd.0008824
    Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.
  3. Synthesis, in vitro antiurease, in vivo antinematodal activity of quinoline analogs and their in-silico study
    Zaman K, Rahim F, Taha M, Sajid M, Hayat S, Nawaz M, et al.
    Bioorg Chem, 2021 10;115:105199.
    PMID: 34329995 DOI: 10.1016/j.bioorg.2021.105199
    Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.
  4. Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study
    Taha M, Alrashedy AS, Almandil NB, Iqbal N, Anouar EH, Nawaz M, et al.
    Int J Biol Macromol, 2021 Nov 01;190:301-318.
    PMID: 34481854 DOI: 10.1016/j.ijbiomac.2021.08.207
    In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.
  5. New biologically dynamic hybrid pharmacophore triazinoindole-based-thiadiazole as potent α-glucosidase inhibitors: In vitro and in silico study
    Khan AA, Rahim F, Taha M, Rehman W, Iqbal N, Wadood A, et al.
    Int J Biol Macromol, 2022 Feb 28;199:77-85.
    PMID: 34968547 DOI: 10.1016/j.ijbiomac.2021.12.147
    Triazinoindole bearing thiadiazole derivatives (1-25) have been synthesized and characterized through different spectroscopic techniques such as 1H, 13C-NMR and HREI-MS. The purpose of the study was to investigate the anti-diabetic activity of the synthesized triazinoindole bearing thiadiazole derivatives by inhibition of α-glucosidase. All synthesized analogues showed outstanding inhibition of α-glucosidase enzyme with IC50 values ranging from 2.5 ± 0.10 to 38.10 ± 0.10 µM as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Analogue 4 (IC50 = 2.5 ± 0.10 µM) was identifies as the most potent analogue in the series with fifteen folds more active than standard acarbose. Structure activity relationship (SAR) studies suggested that α-glucosidase activities of triazinoindole bearing thiadiazole are primarily dependent upon on number and position of different substitutions present on phenyl parts. Molecular docking study were conducted of the optimized compounds (i.e., compound 4, 6, and 3 etc. using MOE default parameters), the results revealed that compound 4, 6, and 3 showed numerous key interactions with the target protein, which indicate the high potential of these compounds against the target compound. All these compounds were screened for cytotoxic activity against normal normal Vero cell line and found non-toxic.
  6. Fulltext Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019
    Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.
    JAMA Oncol, 2022 Mar 01;8(3):420-444.
    PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987
    IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

    OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

    EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).

    FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.

    CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

  7. A feasibility study for the treatment of 1,2-dichloroethane-contaminated groundwater using reedbed system and assessment of its natural attenuation
    Rahim F, Abdullah SRS, Hasan HA, Kurniawan SB, Mamat A, Yusof KA, et al.
    Sci Total Environ, 2022 Mar 25;814:152799.
    PMID: 34982990 DOI: 10.1016/j.scitotenv.2021.152799
    A reedbed system planted with Phragmites australis was implemented to treat chlorinated hydrocarbon-contaminated groundwater in an industrial plant area. Reedbed commissioning was conducted from July 2016 to November 2016 to treat contaminated groundwater via a pump-and-treat mechanism. Combination of horizontal and vertical reedbed systems was applied to treat 1,2-dichloroethane (1,2 DCA) under four parallel installations. The 2-acre horizontal and vertical reedbed systems were designed to treat approximately 305 m3/day of pumped groundwater. Initial concentration of 1,2 DCA was observed at 0.362 mg/L to 4320 mg/L, and the reedbed system successfully reduced the concentration up to 67.9%. The average outlet concentration was measured to be 2.08 mg/L, which was lower than the site-specific target level of 156 mg/L. Natural attenuation analysis was conducted using first-order decay kinetics, showing an average natural attenuation rate of 0.00372/year. Natural attenuation of 1,2 DCA was observed in shallow monitoring wells, which was indicated by the reduction trend of 1,2 DCA concentration, thereby confirming that the reedbed system worked well to remove 1.2 DCA from contaminated groundwater at the shallow profile.
  8. Fulltext Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives
    Hussain R, Ullah H, Rahim F, Sarfraz M, Taha M, Iqbal R, et al.
    Molecules, 2022 Sep 18;27(18).
    PMID: 36144820 DOI: 10.3390/molecules27186087
    Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.
  9. Fulltext A Review of Tracheal Bronchus in Universiti Kebangsaan Malaysia Medical Centre (UKMMC)
    Abdul Rahim F, Goh BS
    Indian J Otolaryngol Head Neck Surg, 2022 Oct;74(Suppl 2):2666-2669.
    PMID: 36452671 DOI: 10.1007/s12070-020-02358-y
    Tracheal bronchus (TB) is a rare congenital anomaly described as a abnormal bronchus that originates directly from the trachea above the carina directed towards the upper lung lobe. We analysed all paediatric rigid endoscopies of the airway from January 2015 until August 2020 to determine the incidence and characteristic of TB. In total, 68 rigid endoscopic airway examination record from children aged 0 to 12 years were analyzed. Endoscopic examination was performed from supraglottic region to carina using a 0 degree Hopkins rod lens telescope. Patients with a TB were identified and the site of TB origin was noted. Data of the identified patients was reviewed for the presence of preoperative airway findings such as stridor, upper lobe pneumonia, other congenital anomalies, intraoperative findings and complications and postoperative general condition outcome. TB was detected in 8 (11.8%) of 68 airway endoscopic examinations. 6 children (75%) were syndromic. 5 patients (62.5%) has congenital malacic airway and 2 patients (25%) has congenital tracheal stenosis. All TB originated from the right lateral wall of the trachea. All children had stridor unrelated to TB as presentation and 4 (50%) of children had preoperative upper lobe pneumonia. Tracheal bronchus is not a rare finding and is highly associated with syndromes and other airway anomalies. Although children with TB can be asymptomatic, upper lobe pneumonia is a common presentation. TB should be included in the differential diagnosis in patients with recurrent right upper lobe pneumonia or collapse and patients with unexplained oxygenation problem during endotracheal intubation, particularly in children with syndromes or other congenital anomalies.
  10. Synthesis of new urease enzyme inhibitors as antiulcer drug and computational study
    Taha M, Ismail S, Imran S, Almandil NB, Alomari M, Rahim F, et al.
    J Biomol Struct Dyn, 2022 Nov;40(18):8232-8247.
    PMID: 33860726 DOI: 10.1080/07391102.2021.1910072
    In search of potent urease inhibitor indole analogues (1-22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1-22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed.Communicated by Ramaswamy H. Sarma.
  11. Fulltext Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018
    Haeuser E, Serfes AL, Cork MA, Yang M, Abbastabar H, Abhilash ES, et al.
    BMC Med, 2022 Dec 19;20(1):488.
    PMID: 36529768 DOI: 10.1186/s12916-022-02639-z
    BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA.

    METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units.

    RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group.

    CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

  12. Synthesis, in vitro biological screening and docking study of benzo[d]oxazole bis Schiff base derivatives as a potent anti-Alzheimer agent
    Taha M, Rahim F, Zaman K, Anouar EH, Uddin N, Nawaz F, et al.
    J Biomol Struct Dyn, 2023 Mar;41(5):1649-1664.
    PMID: 34989316 DOI: 10.1080/07391102.2021.2023640
    We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50 = 0.016 ± 0.12 and 4.5 ± 0.11 µM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC50 = 0.50 ± 0.01, 0.90 ± 0.05 and 0.3 ± 0.05 µM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC50 = 2.70 ± 0.10, 2.60 ± 0.10, 2.20 ± 0.10, 4.25 ± 0.10, 3.30 ± 0.10, 0.96 ± 0.05 and 3.20 ± 0.10 µM) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as 1H-NMR, 13C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma.
  13. New pyrrolopyridine-based thiazolotriazoles as diabetics inhibitors: enzymatic kinetics and in silico study
    Taha M, Rahim F, Hayat S, Chigurupati S, Khan KM, Imran S, et al.
    Future Med Chem, 2023 Mar;15(5):405-419.
    PMID: 37013918 DOI: 10.4155/fmc-2022-0306
    Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 μM and 18.15-71.97 μM, respectively, compared with the reference drug, acarbose (11.98 μM and 12.79 μM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 μM, respectively. The structure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.
  14. Development and Validation of SafeHIT: An Instrument to Assess the Self-Reported Safe Use of Health Information Technology
    Salahuddin L, Ismail Z, Abdul Rahim F, Anawar S, Hashim UR
    Appl Clin Inform, 2023 Aug;14(4):693-704.
    PMID: 37648223 DOI: 10.1055/s-0043-1771394
    BACKGROUND: Implementing health information technology (HIT) may cause unintended consequences and safety risks when incorrectly designed and used. Yet, the tools to assess self-reported safe use of HIT are not well established.

    OBJECTIVE: This study aims to develop and validate SafeHIT, an instrument to assess self-reported safe use of HIT among health care practitioners.

    METHODS: Systematic literature review and a semistructured interview with 31 experts were adopted to generate SafeHIT instrument items. In total, 450 physicians from various departments at three Malaysian public hospitals participated in the questionnaire survey to validate SafeHIT. Exploratory factor analysis and confirmatory factor analysis (CFA) were undertaken to explore the items that best represent a specific construct and to confirm the reliability and validity of the SafeHIT, respectively.

    RESULTS: The final SafeHIT consisted of 14 constructs and 58 items in total. The result of the CFA confirmed that all constructs demonstrated adequate convergent and discriminant validity.

    CONCLUSION: A reliable and valid theoretically underpinned measure of determinants of safe HIT use behavior has been developed. Understanding external factors that influence safe HIT use is useful for developing targeted interventions that favor the quality and safety of health care.

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