Displaying publications 21 - 40 of 157 in total

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  1. Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies
    Taha M, Ullah H, Al Muqarrabun LMR, Khan MN, Rahim F, Ahmat N, et al.
    Bioorg Med Chem, 2018 01 01;26(1):152-160.
    PMID: 29183662 DOI: 10.1016/j.bmc.2017.11.028
    Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.
  2. Carbohydrazones as new class of carbonic anhydrase inhibitors: Synthesis, kinetics, and ligand docking studies
    Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.
    Bioorg Chem, 2017 06;72:89-101.
    PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014
    Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
  3. Chalcones and bis-chalcones: As potential α-amylase inhibitors; synthesis, in vitro screening, and molecular modelling studies
    Tajudeen Bale A, Mohammed Khan K, Salar U, Chigurupati S, Fasina T, Ali F, et al.
    Bioorg Chem, 2018 09;79:179-189.
    PMID: 29763804 DOI: 10.1016/j.bioorg.2018.05.003
    Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05-2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
  4. Coumarin sulfonates: As potential leads for ROS inhibition
    Salar U, Khan KM, Jabeen A, Faheem A, Fakhri MI, Saad SM, et al.
    Bioorg Chem, 2016 12;69:37-47.
    PMID: 27669119 DOI: 10.1016/j.bioorg.2016.09.006
    Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2±9.2μM). Eleven compounds 6 (IC50=46.60±14.6μM), 8 (IC50=11.50±6.5μM), 15 (IC50=21.40±12.2μM), 19 (IC50=5.75±0.86μM), 22 (IC50=10.27±1.06μM), 23 (IC50=33.09±5.61μM), 24 (IC50=4.93±0.58μM), 25 (IC50=21.96±14.74μM), 29 (IC50=12.47±9.2μM), 35 (IC50=20.20±13.4μM) and 37 (IC50=14.47±5.02μM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4-43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed.
  5. Fulltext Crystal structure of (E)-N'-benzyl-idene-2-meth-oxy-benzohydrazide
    Taha M, Baharudin MS, Zaki HM, Yamin BM, Naz H
    Acta Crystallogr Sect E Struct Rep Online, 2014 Sep 01;70(Pt 9):o1071-2.
    PMID: 25309231 DOI: 10.1107/S1600536814019011
    In the title benzoyl-hydrazide derivative, C15H14N2O2, the dihedral angle between the planes of the two phenyl rings is 12.56 (9)°. The azomethine double bond adopts an E configuration stabilized by an N-H⋯O hydrogen bond. In the crystal, the components are linked by C-H⋯O inter-actions to form chains along the b axis.
  6. Fulltext Dentatin Induces Apoptosis in Prostate Cancer Cells via Bcl-2, Bcl-xL, Survivin Downregulation, Caspase-9, -3/7 Activation, and NF-κB Inhibition
    Arbab IA, Looi CY, Abdul AB, Cheah FK, Wong WF, Sukari MA, et al.
    Evid Based Complement Alternat Med, 2012;2012:856029.
    PMID: 23091559 DOI: 10.1155/2012/856029
    This study was set to investigate antiproliferative potential of dentatin (a natural coumarin isolated from Clausena excavata Burm. F) against prostate cancer and to delineate the underlying mechanism of action. Treatment with dentatin dose-dependently inhibited cell growth of PC-3 and LNCaP prostate cancer cell lines, whereas it showed less cytotoxic effects on normal prostate epithelial cell line (RWPE-1). The inhibitory effect of dentatin on prostate cancer cell growth was due to induction of apoptosis as evidenced by Annexin V staining and cell shrinkage. We found that dentatin-mediated accumulation of reactive oxygen species (ROS) and downregulated expression levels of antiapoptotic molecules (Bcl-2, Bcl-xL, and Survivin), leading to disruption of mitochondrial membrane potential (MMP), cell membrane permeability, and release of cytochrome c from the mitochondria into the cytosol. These effects were associated with induction of caspase-9, -3/7 activities, and subsequent DNA fragmentation. In addition, we found that dentatin inhibited TNF-α-induced nuclear translocation of p65, suggesting dentatin as a potential NF-κB inhibitor. Thus, we suggest that dentatin may have therapeutic value in prostate cancer treatment worthy of further development.
  7. Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease
    Alomari M, Taha M, Imran S, Jamil W, Selvaraj M, Uddin N, et al.
    Bioorg Chem, 2019 11;92:103235.
    PMID: 31494327 DOI: 10.1016/j.bioorg.2019.103235
    Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.
  8. Dihydropyrimidones: As novel class of β-glucuronidase inhibitors
    Ali F, Khan KM, Salar U, Iqbal S, Taha M, Ismail NH, et al.
    Bioorg Med Chem, 2016 08 15;24(16):3624-35.
    PMID: 27325448 DOI: 10.1016/j.bmc.2016.06.002
    Dihydropyrimidones 1-37 were synthesized via a 'one-pot' three component reaction according to well-known Biginelli reaction by utilizing Cu(NO3)2·3H2O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC50=28.16±.056μM), 9 (IC50=18.16±0.41μM), 10 (IC50=22.14±0.43μM), 13 (IC50=34.16±0.65μM), 14 (IC50=17.60±0.35μM), 15 (IC50=15.19±0.30μM), 16 (IC50=27.16±0.48μM), 17 (IC50=48.16±1.06μM), 22 (IC50=40.16±0.85μM), 23 (IC50=44.16±0.86μM), 24 (IC50=47.16±0.92μM), 25 (IC50=18.19±0.34μM), 26 (IC50=33.14±0.68μM), 27 (IC50=44.16±0.94μM), 28 (IC50=24.16±0.50μM), 29 (IC50=34.24±0.47μM), 31 (IC50=14.11±0.21μM) and 32 (IC50=9.38±0.15μM) found to be more potent than the standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Molecular docking study was conducted to establish the structure-activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as (1)H, (13)C NMR, EIMS and HREI-MS.
  9. Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management
    Babatunde O, Hameed S, Salar U, Chigurupati S, Wadood A, Rehman AU, et al.
    Mol Divers, 2021 Mar 01.
    PMID: 33650031 DOI: 10.1007/s11030-021-10196-5
    A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02-88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12-89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.
  10. Energy balance and life cycle assessments in producing microalgae biodiesel via a continuous microalgal-bacterial photobioreactor loaded with wastewater
    Leong WH, Lim JW, Rawindran H, Liew CS, Lam MK, Ho YC, et al.
    Chemosphere, 2023 Nov;341:139953.
    PMID: 37634592 DOI: 10.1016/j.chemosphere.2023.139953
    Life cycle assessments of microalgal cultivation systems are often conducted to evaluate the sustainability and feasibility factors of the entire production chain. Unlike widely reported conventional microalgal cultivation systems, the present work adopted a microalgal-bacterial cultivation approach which was upscaled into a pilot-scale continuous photobioreactor for microalgal biomass production into biodiesel from wastewater resources. A multiple cradle-to-cradle system ranging from microalgal biomass-to-lipid-to-biodiesel was evaluated to provide insights into the energy demand of each processes making up the microalgae-to-biodiesel value chain system. Energy feasibility studies revealed positive NER values (4.95-8.38) for producing microalgal biomass but deficit values for microalgal-to-biodiesel (0.14-0.23), stemming from the high energy input requirements in the downstream processes for converting biomass into lipid and biodiesel accounting to 88-90% of the cumulative energy demand. Although the energy balance for microalgae-to-biodiesel is in the deficits, it is comparable with other reported biodiesel production case studies (0.12-0.40). Nevertheless, the approach to using microalgal-bacterial cultivation system has improved the overall energy efficiency especially in the upstream processes compared to conventional microalgal cultivation systems. Energy life cycle assessments with other microalgal based biofuel systems also proposed effective measures in increasing the energy feasibility either by utilizing the residual biomass and less energy demanding downstream extraction processes from microalgal biomass. The microalgal-bacterial cultivation system is anticipated to offer both environmental and economic prospects for upscaling by effectively exploiting the low-cost nutrients from wastewaters via bioconversion into valuable microalgal biomass and biodiesel.
  11. 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.
  12. Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions
    Taha M, Ismail NH, Javaid K, Imran S, Anouar el H, Wadood A, et al.
    Bioorg Chem, 2015 Dec;63:24-35.
    PMID: 26398141 DOI: 10.1016/j.bioorg.2015.09.001
    2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.
  13. Evaluation of bisindole as potent β-glucuronidase inhibitors: synthesis and in silico based studies
    Khan KM, Rahim F, Wadood A, Taha M, Khan M, Naureen S, et al.
    Bioorg Med Chem Lett, 2014 Apr 1;24(7):1825-9.
    PMID: 24602903 DOI: 10.1016/j.bmcl.2014.02.015
    Bisindole analogs 1-17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50=1.62±0.04 μM), 6 (IC50=1.86±0.05 μM), 10 (IC50=2.80±0.29 μM), 9 (IC50=3.10±0.28 μM), 14 (IC50=4.30±0.08 μM), 2 (IC50=18.40±0.09 μM), 19 (IC50=19.90±1.05 μM), 4 (IC50=20.90±0.62 μM), 7 (IC50=21.50±0.77 μM), and 3 (IC50=22.30±0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50=48.40±1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.
  14. Exploring efficacy of indole-based dual inhibitors for α-glucosidase and α-amylase enzymes: In silico, biochemical and kinetic studies
    Kawde AN, Taha M, Alansari RS, Almandil NB, Anouar EH, Uddin N, et al.
    Int J Biol Macromol, 2020 Jul 01;154:217-232.
    PMID: 32173438 DOI: 10.1016/j.ijbiomac.2020.03.090
    α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1-18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.
  15. Fundamental alteration of cellular biochemicals from attached microalgae onto palm kernel expeller waste upon optimizing the growth environment in forming adhesion complex
    Rawindran H, Khoo KS, Ethiraj B, Suparmaniam U, Leong WH, Raksasat R, et al.
    Environ Res, 2023 Sep 15;233:116533.
    PMID: 37394167 DOI: 10.1016/j.envres.2023.116533
    Changing the growth environment for microalgae can overall lead to the fundamental alteration in cellular biochemicals whilst attaching onto palm kernel expeller (PKE) waste to form adhesion complex in easing harvesting at stationary growth phase. This study had initially optimized the PKE dosage, light intensity and photoperiod in maximizing the attached microalgal productivity being attained at 0.72 g/g day. Lipid content increased progressively from pH 3 to pH 11, with the highest value observed at pH 11. Meanwhile, in terms of protein and carbohydrate contents, the highest values were obtained by cultivation medium of pH 5 with 9.92 g and 17.72 g, respectively followed by pH 7 with 9.16 g and 16.36 g, respectively. Moreover, the findings also suggested that the low pH mediums utilized polar interactions in the formation of complexes between PKE and microalgae, whereas at higher pH levels, the non-polar interactions became more significant. The work of attachment was thermodynamically favourable towards the attachment formation with values greater than zero which was also aligned with the microscopic surface topography, i.e., revealing a clustering pattern of microalgae colonizing the PKE surface. These findings contribute to comprehensive understanding of optimizing growth condition and harvesting strategy of attached microalgae in attaining the cellular biochemical components, facilitating the development of efficient and sustainable bioresource utilization.
  16. Hybrid benzothiazole analogs as antiurease agent: Synthesis and molecular docking studies
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Khan KM, et al.
    Bioorg Chem, 2016 Jun;66:80-7.
    PMID: 27038849 DOI: 10.1016/j.bioorg.2016.03.010
    Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.
  17. Hydrazinyl arylthiazole based pyridine scaffolds: Synthesis, structural characterization, in vitro α-glucosidase inhibitory activity, and in silico studies
    Ali F, Khan KM, Salar U, Taha M, Ismail NH, Wadood A, et al.
    Eur J Med Chem, 2017 Sep 29;138:255-272.
    PMID: 28672278 DOI: 10.1016/j.ejmech.2017.06.041
    Acarbose, miglitol, and voglibose are the inhibitors of α-glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α-glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1-39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, (1)H-, and (13)C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α-glucosidase inhibitory activity and found many folds active (IC50 = 1.40 ± 0.01-236.10 ± 2.20 μM) as compared to the standard acarbose having IC50 value of 856.45 ± 5.60 μM. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO2) which have negative inductive effect were found to make important interactions with active site residues.
  18. Fulltext Improvement in medically certified death: results from a pilot study in the state of Malacca, Malaysia
    Faudzi AY, Amal NM, Zainal AO, Lailanor I, Sirajuddin H, Taha MA
    Med J Malaysia, 2011 Mar;66(1):32-5.
    PMID: 23765140 MyJurnal
    A systematic approach to death registration and reporting is essential for studies and comparison within or between countries. One of the accepted methods in the system is to have medically certified death. The objective of this study was to improve the proportion of medically certified death (MCD) in the state of Malacca. Structured questionnaires were used by Medical Assistants (MAs) in the investigation of the cause of death for non-medically certified deaths. Data on certification of death by MAs in Malacca was analysed and compared with the total deaths obtained from the Department of Statistics. Possible determinants of deaths were investigated. Total deaths in the state of Malacca during the study period from 2000 - 2001 were 5941. About 35% (883/2493) of the total deaths in year 2000 and 45% (1550/3448) in 2001 certified by MAs were examined. By districts, 50.6% were certified in the district of Malacca Tengah, 13.4% Jasin and 36.0% Alor Gajah in 2000; 65.9% occurred in Malacca Tengah, 11.0% Jasin and 23.2% Alor Gajah in 2001. This project helped to increase the percentage of the medically certified deaths in Malacca from 49.8% in year 1998, 49% in 1999 to 73% in 2000 and 85% in 2001. The proportion of MCD in Malacca in 2000 (73%) may be increased to 93% if all MCDs done by MAs were accepted by the Department of Statistics. There is still a high proportion (23.6%) of ill-defined conditions such as old age and sudden death being diagnosed by MAs. The study shows that the quality of mortality data particularly in the percentage of medically certified deaths can be improved.
  19. In Vitro Cytotoxicity and Anti-inflammatory Cytokinine Activity Study of Three Isolated Novel Compounds of Prismatomeris glabra
    Alkadi KAA, Ashraf K, Adam A, Shah SAA, Taha M, Hasan MH, et al.
    J Pharm Bioallied Sci, 2020 12 21;13(1):116-122.
    PMID: 34084057 DOI: 10.4103/jpbs.JPBS_279_19
    Objectives: The aim of the present study was to isolate and evaluate cytotoxicity and anti-inflammatory activities of new novel compounds isolated from Prismatomeris glabra.

    Materials and Methods: Dried root of P. glabra was extracted under reflux with methyl alcohol, fractionated through the vacuum liquid chromatography technique, and evaporated and then purified the compounds using column chromatography and preparative thin-layer chromatography. THP-1 cells were treated with amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol with various concentrations (0-30 µg/mL) and then incubated with MTS reagent for 2h. Treatment was done for 24, 48, and 72h. Then, effects of these compounds were also tested on PGE2, TNF-α, and IL-6 expression in human THP-1-derived macrophage cells for 24h.

    Results: Three new compounds such as amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol were isolated. After 24h of incubation, a significant decrease in cell viability was reported with IC50 values of amentoflavone, 5,7,4'- hydroxyflavonoid, and stigmasterol (21 µg/mL ≡ 38 M), (18 µg/mL ≡ 66 M) and (20 µg/mL ≡ 48.5 M), respectively. Whereas for 48 and 72h treatment showed a less decreased cell viability compared with 24h treatment. These compounds also showed a significant reduction in the production of TNF-α, IL-6, and PGE2 in a dose-dependent manner.

    Conclusions: The isolated new compounds showed significant cytotoxicity and anti-inflammatory effects.

  20. In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
    Taha M, Ismail NH, Imran S, Rahim F, Wadood A, Al Muqarrabun LM, et al.
    Bioorg Chem, 2016 10;68:80-9.
    PMID: 27474803 DOI: 10.1016/j.bioorg.2016.07.010
    Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX.
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