Displaying publications 81 - 100 of 166 in total

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  1. Maxillofacial trauma with emphasis on soft-tissue injuries in Malaysia
    Hussaini HM, Rahman NA, Rahman RA, Nor GM, Ai Idrus SM, Ramli R
    Int J Oral Maxillofac Surg, 2007 Sep;36(9):797-801.
    PMID: 17630250
    Soft-tissue injuries with or without facial bone involvement are the most common presentation following maxillofacial trauma. The objective of this study was to look at the distribution, pattern and type of soft-tissue injury in relation to aetiology. Records of patients over a period of 5 years (1998-2002), who sustained maxillofacial injuries and were treated at Kajang Hospital, a secondary referral hospital, were reviewed. Out of 313 patients with maxillofacial injuries, 295 patients sustained soft-tissue injuries. Males (79%) between 21 and 30 years old (34%) were the majority of patients. Road-traffic accident was the main cause of soft-tissue injuries (75%) with motorcycle accident being the most frequent (40%). The upper lips (23%) and the lower lips (18%) were the most common extraoral site involved, while the labial mucosa and sulcular areas, both accounting for 21%, were the most common intraoral sites. Stringent road-traffic regulations should be practiced in developing countries, as morbidity arising from road-traffic accidents poses a national economic and social problem.
  2. Fulltext Validation of quantitative structure-activity relationship (QSAR) model for photosensitizer activity prediction
    Frimayanti N, Yam ML, Lee HB, Othman R, Zain SM, Rahman NA
    Int J Mol Sci, 2011;12(12):8626-44.
    PMID: 22272096 DOI: 10.3390/ijms12128626
    Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r(2) value, r(2) (CV) value and r(2) prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC(50) values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r(2) prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.
  3. Fulltext Design of new competitive dengue NS2B/NS3 protease inhibitors-a computational approach
    Frimayanti N, Chee CF, Zain SM, Rahman NA
    Int J Mol Sci, 2011;12(2):1089-100.
    PMID: 21541045 DOI: 10.3390/ijms12021089
    Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A) and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA). The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy) were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA) with various substituents.
  4. Polyethylene glycol-coated porous magnetic nanoparticles for targeted delivery of chemotherapeutics under magnetic hyperthermia condition
    Dabbagh A, Hedayatnasab Z, Karimian H, Sarraf M, Yeong CH, Madaah Hosseini HR, et al.
    Int J Hyperthermia, 2019;36(1):104-114.
    PMID: 30428737 DOI: 10.1080/02656736.2018.1536809
    PURPOSE: Although magnetite nanoparticles (MNPs) are promising agents for hyperthermia therapy, insufficient drug encapsulation efficacies inhibit their application as nanocarriers in the targeted drug delivery systems. In this study, porous magnetite nanoparticles (PMNPs) were synthesized and coated with a thermosensitive polymeric shell to obtain a synergistic effect of hyperthermia and chemotherapy.

    MATERIALS AND METHODS: PMNPs were produced using cetyltrimethyl ammonium bromide template and then coated by a polyethylene glycol layer with molecular weight of 1500 Da (PEG1500) and phase transition temperature of 48 ± 2 °C to endow a thermosensitive behavior. The profile of drug release from the nanostructure was studied at various hyperthermia conditions generated by waterbath, magnetic resonance-guided focused ultrasound (MRgFUS), and alternating magnetic field (AMF). The in vitro cytotoxicity and hyperthermia efficacy of the doxorubicin-loaded nanoparticles (DOX-PEG1500-PMNPs) were assessed using human lung adenocarcinoma (A549) cells.

    RESULTS: Heat treatment of DOX-PEG1500-PMNPs containing 235 ± 26 mg·g-1 DOX at 48 °C by waterbath, MRgFUS, and AMF, respectively led to 71 ± 4%, 48 ± 3%, and 74 ± 5% drug release. Hyperthermia treatment of the A549 cells using DOX-PEG1500-PMNPs led to 77% decrease in the cell viability due to the synergistic effects of magnetic hyperthermia and chemotherapy.

    CONCLUSION: The large pores generated in the PMNPs structure could provide a sufficient space for encapsulation of the chemotherapeutics as well as fast drug encapsulation and release kinetics, which together with thermosensitive characteristics of the PEG1500 shell, make DOX-PEG1500-PMNPs promising adjuvants to the magnetic hyperthermia modality.

  5. A clinical evaluation of bleeding patterns, adverse effects, and satisfaction with the subdermal etonogestrel implant among postpartum and non-postpartum users
    Wahab NA, Rahman NA, Mustafa KB, Awang M, Sidek AA, Ros RM
    Int J Gynaecol Obstet, 2016 Feb;132(2):237-8.
    PMID: 26617248 DOI: 10.1016/j.ijgo.2015.07.022
  6. Antiviral actions of flavanoid-derived compounds on dengue virus type-2
    Muhamad M, Kee LY, Rahman NA, Yusof R
    Int J Biol Sci, 2010 May 23;6(3):294-302.
    PMID: 20567498
    Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
  7. Recent advances in celluloses and their hybrids for stimuli-responsive drug delivery
    Sampath Udeni Gunathilake TM, Ching YC, Chuah CH, Rahman NA, Liou NS
    Int J Biol Macromol, 2020 May 07;158:670-688.
    PMID: 32389655 DOI: 10.1016/j.ijbiomac.2020.05.010
    The limitations of existing drug delivery systems (DDS) such as non-specific bio-distribution and poor selectivity have led to the exploration of a variety of carrier platforms to facilitate highly desirable and efficient drug delivery. Stimuli-responsive DDS are one of the most versatile and innovative approach to steer the compounds to the intended sites by exploiting their responsiveness to a range of various triggers. Preparation of stimuli-responsive DDS using celluloses and their derivatives offer a remarkable advantage over conventional polymer materials. In this review, we highlight on state-of-art progress in developing cellulose/cellulose hybrid stimuli-responsive DDS, which covers the preparation techniques, physicochemical properties, basic principles and, mechanisms of stimuli effect on drug release from various types of cellulose based carriers, through recent innovative investigations. Attention has been paid to endogenous stimuli (pH, temperature, redox gradient and ionic-strength) responsive DDS and exogenous stimuli (light, magnetic field and electric field) responsive DDS, where the cellulose-based materials have been extensively employed. Furthermore, the current challenges and future prospects of these DDS are also discussed at the end.
  8. Work-related musculoskeletal symptoms and coping strategies among dental auxiliaries at hospital universiti Sains Malaysia
    Rahman NA, Adnan MM, Yusoff A, Shu JMH, Rustam K
    Indian J Dent Res, 2020 4 5;31(1):61-66.
    PMID: 32246684 DOI: 10.4103/ijdr.IJDR_430_18
    Background: Dental personnel are vulnerable to work-related musculoskeletal symptoms (WMSS) due to the nature of their profession.

    Aim: To determine WMSS experienced by dental auxiliaries and their coping strategies toward these symptoms.

    Setting and Design: A cross-sectional study was conducted on 82 dental auxiliaries at a university dental hospital in Malaysia.

    Materials and Methods: Nordic musculoskeletal questionnaire and the Brief COPE questionnaire were used to measure the musculoskeletal symptoms and coping strategies of the respondents, respectively. Data were analyzed using IBM SPSS version 22.0.

    Results: Dental auxiliaries consisted of dental staff nurses (30.5%), dental surgery assistants (40.2%), dental technologists (18.3%), and healthcare assistants (11.0%). Their mean [standard deviation (SD)] age was 33.4 (7.60) years. Most of the respondents had been troubled with ache, pain, and discomfort at the neck, 54.9% (95% confidence interval 44.0%, 66.0%]. In addition, they were troubled mainly with distress at the low back (34.1%) and the ankle or feet (34.1%) which had prevented the respondents from doing their regular job over the past 12 months. The most common areas that had troubled the respondents over the past 7 days were the neck (36.6%), low back (36.6%), and ankle or feet (36.6%). The coping strategy most commonly practiced by the respondents was religion with a mean (SD) score of 3.70 (2.15), followed by active coping [3.13 (0.68)] and acceptance [3.13 (0.69)].

    Conclusion: The prevalence of WMSS was high in the dental auxiliaries particularly in the neck region. The most common coping strategy used was religion. Awareness programs on the prevention of WMSS among the dental auxiliaries should be increased.

  9. Analysis of secondary structure predictions of dengue virus type 2 NS2B/NS3 against crystal structure to evaluate the predictive power of the in silico methods
    Othman R, Wahab HA, Yusof R, Rahman NA
    In Silico Biol. (Gedrukt), 2007;7(2):215-24.
    PMID: 17688447
    Multiple sequence alignment was performed against eight proteases from the Flaviviridae family using ClustalW to illustrate conserved domains. Two sets of prediction approaches were applied and the results compared. Firstly, secondary structure prediction was performed using available structure prediction servers. The second approach made use of the information on the secondary structures extracted from structure prediction servers, threading techniques and DSSP database of some of the templates used in the threading techniques. Consensus on the one-dimensional secondary structure of Den2 protease was obtained from each approach and evaluated against data from the recently crystallised Den2 NS2B/NS3 obtained from the Protein Data Bank (PDB). Results indicated the second approach to show higher accuracy compared to the use of prediction servers only. Thus, it is plausible that this approach is applicable to the initial stage of structural studies of proteins with low amino acid sequence homology against other available proteins in the PDB.
  10. Fulltext Development of a NS2B/NS3 protease inhibition assay using AlphaScreen® beads for screening of anti-dengue activities
    Abduraman MA, Hariono M, Yusof R, Rahman NA, Wahab HA, Tan ML
    Heliyon, 2018 Dec;4(12):e01023.
    PMID: 30560214 DOI: 10.1016/j.heliyon.2018.e01023
    Background: Dengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities.

    Methods: The assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format.

    Results: The optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable z' factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities.

    Conclusion: The AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.

  11. Fulltext Effects of Low-Level Laser Therapy and Bracket Systems on Root Resorption during Orthodontic Treatment: A Randomized Clinical Trial
    Shahid F, Nowrin SA, Alam MK, Khamis MF, Husein A, Rahman NA
    Healthcare (Basel), 2023 Mar 15;11(6).
    PMID: 36981521 DOI: 10.3390/healthcare11060864
    This study aimed to assess the outcomes of low-level laser therapy (LLLT) with the conventional bracket (CB) and self-ligating (SL) bracket systems on root resorption (RR) during orthodontic treatment. A total of 32 patients were included in this randomized clinical trial. All the patients were randomly divided into four individual groups (SLL: self-ligating laser, CBL: conventional bracket laser, SLNL: self-ligating non-laser, CBNL: conventional bracket non-laser). RR was measured from the cone-beam computed tomography (CBCT) radiographs which were taken at two stages of the orthodontic treatment: pre-treatment (T1) and after leveling and alignment stage (T2). Wilcoxon rank test for the comparison was conducted to compare the RR at T1 and T2 stages within each group and showed a significant difference (p < 0.05) for various variables. Mann Whitney test compared the RR in laser and non-laser groups irrespective of the bracket systems and exhibited no significant differences except the left lateral incisor. Moreover, CB and SL groups showed no significant difference in RR among any tooth. Kruskal Wallis test was performed to compare the RR among all groups which presented no significant differences. LLLT and bracket systems have no consequences on RR until the leveling and alignment stage of orthodontic treatment.
  12. Anti-inflammatory trends of new benzimidazole derivatives
    Bukhari SN, Lauro G, Jantan I, Fei Chee C, Amjad MW, Bifulco G, et al.
    Future Med Chem, 2016 Oct;8(16):1953-1967.
    PMID: 27654499
    In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A2, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-α and IL-6 in mouse RAW264.7 macrophages.
  13. Fulltext Taxon- and Growth Phase-Specific Antioxidant Production by Chlorophyte, Bacillariophyte, and Haptophyte Strains Isolated From Tropical Waters
    Rahman NA, Katayama T, Wahid MEA, Kasan NA, Khatoon H, Yamada Y, et al.
    Front Bioeng Biotechnol, 2020;8:581628.
    PMID: 33330417 DOI: 10.3389/fbioe.2020.581628
    Antioxidants found in microalgae play an essential role in both animals and humans, against various diseases and aging processes by protecting cells from oxidative damage. In this study, 26 indigenous tropical marine microalgae were screened. Out of the 26 screened strains, 10 were selected and were further investigated for their natural antioxidant compounds which include carotenoids, phenolics, and fatty acids collected in their exponential and stationary phases. The antioxidant capacity was also evaluated by a total of four assays, which include ABTS, DPPH, superoxide radical (O2•-) scavenging capacity, and nitric oxide (•NO-) scavenging capacity. This study revealed that the antioxidant capacity of the microalgae varied between divisions, strains, and growth phase and was also related to the content of antioxidant compounds present in the cells. Carotenoids and phenolics were found to be the major contributors to the antioxidant capacity, followed by polyunsaturated fatty acids linoleic acid (LA), eicosapentaenoic acid (EPA), arachidonic acid (ARA), and docosahexaenoic acid (DHA) compared to other fatty acids. The antioxidant capacity of the selected bacillariophytes and haptophytes was found to be positively correlated to phenolic (R2-value = 0.623, 0.714, and 0.786 with ABTS, DPPH, and •NO-) under exponential phase, and to carotenoid fucoxanthin and β-carotene (R2 value = 0.530, 0.581 with ABTS, and 0.710, 0.795 with O2•-) under stationary phase. Meanwhile, antioxidant capacity of chlorophyte strains was positively correlated with lutein, β-carotene and zeaxanthin under the exponential phase (R2 value = 0.615, 0.615, 0.507 with ABTS, and R2 value = 0.794, 0.659, and 0.509 with •NO-). In the stationary phase, chlorophyte strains were positively correlated with violaxanthin (0.755 with •NO-), neoxanthin (0.623 with DPPH, 0.610 with •NO-), and lutein (0.582 with •NO-). This study showed that antioxidant capacity and related antioxidant compound production of tropical microalgae strains are growth phase-dependent. The results can be used to improve the microalgal antioxidant compound production for application in pharmaceutical, nutraceutical, food, and feed industry.
  14. Phosphodiesterase-5 inhibitors and their analogues as adulterants of herbal and food products: analysis of the Malaysian market, 2014-16
    Bujang NB, Chee CF, Heh CH, Rahman NA, Buckle MJC
    Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2017 Jul;34(7):1101-1109.
    PMID: 28580889 DOI: 10.1080/19440049.2017.1336674
    Adulteration of herbal health supplements with phosphodiesterase-5 (PDE-5) inhibitors and their analogues is becoming a worldwide problem. The aim of this study was to investigate herbal and food products sold in the Malaysian market for the presence of these adulterants. Sixty-two products that claim to enhance men's sexual health were sampled between April 2014 and April 2016. These products included unregistered products seized by the Pharmacy Enforcement Division of the Ministry of Health (n = 39), products sent to the National Pharmaceutical Regulatory Agency for pre-registration testing (n = 9) and products investigated under the post-registration market surveillance programme (n = 14). The products were tested against an in-house spectral library consisting of 61 PDE-5 inhibitors and analogues using a validated liquid chromatography-mass spectrometry ion-trap-time-of-flight (LC-MS IT-TOF) method. Thirty-two (82%) of the unregistered products and two (14%) of the registered products were found to be adulterated with at least one PDE-5 inhibitor or analogue, while none of the pre-registration products contained adulterants. A total of 16 different adulterants were detected and 36% of the adulterated products contained a mixture of two or more adulterants. This study has demonstrated that the adulteration of unregistered herbal products in the Malaysian market is an alarming issue that needs to be urgently addressed by the relevant authorities.
  15. Lung cancer: active therapeutic targeting and inhalational nanoproduct design
    Alhajj N, Chee CF, Wong TW, Rahman NA, Abu Kasim NH, Colombo P
    Expert Opin Drug Deliv, 2018 12;15(12):1223-1247.
    PMID: 30422017 DOI: 10.1080/17425247.2018.1547280
    INTRODUCTION: Pulmonary drug delivery is organ-specific and benefits local drug action for lung cancer. The use of nanotechnology and targeting ligand enables cellular-specific drug action. Combination approaches increase therapeutic efficacy and reduce adverse effects of cancer chemotherapeutics that have narrow therapeutic index window and high cytotoxicity levels. The current progress of inhaled cancer chemotherapeutics has not been examined with respect to targeting strategy and clinical application potential.

    AREAS COVERED: This review examines the state of the art in passive (processing and formulation) and active (targeting ligand and receptor binding) technologies in association with the use of nanocarrier to combat lung cancer. It highlights routes to equip nanocarrier with targeting ligands as a function of the chemistry of participating biomolecules and challenges in inhalational nanoproduct development and clinical applications. Both research and review articles were examined using the Scopus, Elsevier, Web of Science, Chemical Abstracts, Medline, CASREACT, CHEMCATS, and CHEMLIST database with the majority of information retrieved between those of 2000-2018.

    EXPERT COMMENTARY: The therapeutic efficacy of targeting ligand-decorated nanocarriers needs to be demonstrated in vivo in the form of finished inhalational products. Their inhalation efficiency and medical responses require further examination. Clinical application of inhaled nanocancer chemotherapeutics is premature.

  16. Fulltext Distribution of Flavonoids and Cyclohexenyl Chalcone Derivatives in Conventional Propagated and In Vitro-Derived Field-Grown Boesenbergia rotunda (L.) Mansf
    Tan BC, Tan SK, Wong SM, Ata N, Rahman NA, Khalid N
    Evid Based Complement Alternat Med, 2015;2015:451870.
    PMID: 25883671 DOI: 10.1155/2015/451870
    The distribution patterns of flavonoids and cyclohexenyl chalcone derivatives in conventional propagated (CP) and in vitro-derived (CPA) field-grown plants of an important medicinal ginger, Boesenbergia rotunda, are described. A total of eight compounds were extracted from six organs (rootlet, rhizome, shoot base, maroon stem, stalk, and leaf) of the CP and CPA plants. Five major chromatographic peaks, namely, alpinetin, pinocembrin, pinostrobin, 4-hydroxypanduratin A, and panduratin A, were consistently observed by high performance liquid chromatography. Nonaerial organs had higher levels of flavonoids than the aerial ones for all types of samples. Among the compounds detected, pinostrobin and 4-hydroxypanduratin A were the most abundant flavonoid and cyclohexenyl chalcone derivative, respectively. The distribution and abundance of the bioactive compounds suggested that the shoot base could be more potentially useful for medicinal application than other organs of the plant and may be the site of storage or occurrence of biosynthetic enzymatic activities.
  17. Facial Fractures in Kajang Hospital, Malaysia: A 5-Year Review
    Rahman RA, Hussaini HM, Rahman NA, Rahman SR, Nor GM, Ai Idrus SM, et al.
    Eur J Trauma Emerg Surg, 2007 Feb;33(1):90-5.
    PMID: 26815981 DOI: 10.1007/s00068-007-5154-5
    The objective of this study was to determine the demographic data as well as other relevant data pertaining to the management of patients with maxillofacial injury in a Malaysian government regional hospital.
  18. PASS-assisted design, synthesis and antioxidant evaluation of new butylated hydroxytoluene derivatives
    Ariffin A, Rahman NA, Yehye WA, Alhadi AA, Kadir FA
    Eur J Med Chem, 2014 Nov 24;87:564-77.
    PMID: 25299680 DOI: 10.1016/j.ejmech.2014.10.001
    New multipotent antioxidants (MPAOs), namely 1,3,4-thiadiazoles and 1,2,4-triazoles bearing the well-known free radical scavenger butylated hydroxytoluene (BHT), were designed and synthesized using an acid-(base-) catalyzed intramolecular dehydrative cyclization reaction of the corresponding 1-acylthiosemicarbazides. The structure-activity relationship (SAR) of the designed antioxidants was performed along with the prediction of activity spectra for substances (PASS) training set. Experimental studies based on antioxidant activity using DPPH and lipid peroxidation assays verified the predictions obtained by the PASS-assisted design strategy. Compounds 4a-b, 5a-b and 6a-b showed an inhibition of stable DPPH free radicals at a 10(-4) M more than the well-known standard antioxidant BHT. Compounds with p-methoxy substituents (4b, 5b and 6b) were more active than o-methoxy substituents (4a, 5a and 6a). With an IC50 of 2.85 ± 1.09 μM, compound 6b exhibited the most promising in vitro inhibition of lipid peroxidation, inhibiting Fe(2+)-induced lipid peroxidation of essential oils derived from the egg yolk-based lipid-rich medium by 86.4%. The parameters for the drug-likeness of these BHT derivatives were also evaluated according to Lipinski's 'rule-of-five'. All of the BHT derivatives were found to violate one of Lipinski's parameters (Log P ≥ 5) even though they have been found to be soluble in protic solvents. The predictive TPSA and %ABS data allow for the conclusion that these compounds could have a good capacity for penetrating cell membranes. Therefore, these novel MPAOs containing lipophilic and hydrophilic groups can be proposed as potential antioxidants for tackling oxidative stress and lipid peroxidation processes.
  19. Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors
    Takhi M, Sreenivas K, Reddy CK, Munikumar M, Praveena K, Sudheer P, et al.
    Eur J Med Chem, 2014 Sep 12;84:382-94.
    PMID: 25036796 DOI: 10.1016/j.ejmech.2014.07.036
    A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.
  20. Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review
    Yehye WA, Rahman NA, Ariffin A, Abd Hamid SB, Alhadi AA, Kadir FA, et al.
    Eur J Med Chem, 2015 Aug 28;101:295-312.
    PMID: 26150290 DOI: 10.1016/j.ejmech.2015.06.026
    Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure-activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.
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