Displaying publications 1 - 20 of 45 in total

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  1. Fulltext Effect of alcohol structure on the optimum condition for novozym 435-catalyzed synthesis of adipate esters
    Abdul Rahman MB, Chaibakhsh N, Basri M
    Biotechnol Res Int, 2011;2011:162987.
    PMID: 22389769 DOI: 10.4061/2011/162987
    Immobilized Candida antarctica lipase B, Novozym 435, was used as the biocatalyst in the esterification of adipic acid with four different isomers of butanol (n-butanol, sec-butanol, iso-butanol, and tert-butanol). Optimum conditions for the synthesis of adipate esters were obtained using response surface methodology approach with a four-factor-five-level central composite design concerning important reaction parameters which include time, temperature, substrate molar ratio, and amount of enzyme. Reactions under optimized conditions has yielded a high percentage of esterification (>96%) for n-butanol, iso-butanol, and sec-butanol, indicating that extent of esterification is independent of the alcohol structure for primary and secondary alcohols at the optimum conditions. Minimum reaction time (135 min) for achieving maximum ester yield was obtained for iso-butanol. The required time for attaining maximum yield and also the initial rates in the synthesis of di-n-butyl and di-sec-butyl adipate were nearly the same. Immobilized Candida antarctica lipase B was also capable of esterifying tert-butanol with a maximum yield of 39.1%. The enzyme is highly efficient biocatalyst for the synthesis of adipate esters by offering a simple production process and a high esterification yield.
  2. An insight into structure and stability of DNA in ionic liquids from molecular dynamics simulation and experimental studies
    Jumbri K, Abdul Rahman MB, Abdulmalek E, Ahmad H, Micaelo NM
    Phys Chem Chem Phys, 2014 Jul 21;16(27):14036-46.
    PMID: 24901033 DOI: 10.1039/c4cp01159g
    Molecular dynamics simulation and biophysical analysis were employed to reveal the characteristics and the influence of ionic liquids (ILs) on the structural properties of DNA. Both computational and experimental evidence indicate that DNA retains its native B-conformation in ILs. Simulation data show that the hydration shells around the DNA phosphate group were the main criteria for DNA stabilization in this ionic media. Stronger hydration shells reduce the binding ability of ILs' cations to the DNA phosphate group, thus destabilizing the DNA. The simulation results also indicated that the DNA structure maintains its duplex conformation when solvated by ILs at different temperatures up to 373.15 K. The result further suggests that the thermal stability of DNA at high temperatures is related to the solvent thermodynamics, especially entropy and enthalpy of water. All the molecular simulation results were consistent with the experimental findings. The understanding of the properties of IL-DNA could be used as a basis for future development of specific ILs for nucleic acid technology.
  3. Molecular dynamics of thermoenzymes at high temperature and pressure: a review
    Abedi Karjiban R, Lim WZ, Basri M, Abdul Rahman MB
    Protein J, 2014 Aug;33(4):369-76.
    PMID: 24871480 DOI: 10.1007/s10930-014-9568-8
    Lipases are known for their versatility in addition to their ability to digest fat. They can be used for the formulation of detergents, as food ingredients and as biocatalysts in many industrial processes. Because conventional enzymes are frangible at high temperatures, the replacement of conventional chemical routes with biochemical processes that utilize thermostable lipases is vital in the industrial setting. Recent theoretical studies on enzymes have provided numerous fundamental insights into the structures, folding mechanisms and stabilities of these proteins. The studies corroborate the experimental results and provide additional information regarding the structures that were determined experimentally. In this paper, we review the computational studies that have described how temperature affects the structure and dynamics of thermoenzymes, including the thermoalkalophilic L1 lipase derived from Bacillus stearothermophilus. We will also discuss the potential of using pressure for the analysis of the stability of thermoenzymes because high pressure is also important for the processing and preservation of foods.
  4. Modeling and optimization of lipase-catalyzed production of succinic acid ester using central composite design analysis
    Abdul Rahman MB, Jarmi NI, Chaibakhsh N, Basri M
    J Ind Microbiol Biotechnol, 2011 Jan;38(1):229-34.
    PMID: 20803246 DOI: 10.1007/s10295-010-0817-3
    Esterification of succinic acid with oleyl alcohol catalyzed by immobilized Candida antarctica lipase B (Novozym 435) was investigated in this study. Response surface methodology (RSM) based on a five-level, four-variable central composite design (CCD) was used to model and analyze the reaction. A total of 21 experiments representing different combinations of the four parameters including temperature (35-65°C), time (30-450 min), enzyme amount (20-400 mg), and alcohol:acid molar ratio (1:1-8:1) were generated. A partial cubic equation could accurately model the response surface with a R(2) of 0.9853. The effect and interactions of the variables on the ester synthesis were also studied. Temperature was found to be the most significant parameter that influenced the succinate ester synthesis. At the optimal conditions of 41.1°C, 272.8 min, 20 mg enzyme amount and 7.8:1 alcohol:acid molar ratio, the esterification percentage was 85.0%. The model can present a rapid means for estimating the conversion yield of succinate ester within the selected ranges.
  5. Anticancer activity of 3-O-acylated betulinic acid derivatives obtained by enzymatic synthesis
    Ahmad FB, Ghaffari Moghaddam M, Basri M, Abdul Rahman MB
    Biosci Biotechnol Biochem, 2010;74(5):1025-9.
    PMID: 20460723
    An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC(50)<10 microg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.
  6. Binding of tetrabutylammonium bromide based deep eutectic solvent to DNA by spectroscopic analysis
    Yusof R, Jumbri K, Ahmad H, Abdulmalek E, Abdul Rahman MB
    Spectrochim Acta A Mol Biomol Spectrosc, 2021 May 15;253:119543.
    PMID: 33636491 DOI: 10.1016/j.saa.2021.119543
    The binding characteristics of DNA in deep eutectic solvents (DESs), particularly the binding energy and interaction mechanism, are not widely known. In this study, the binding of tetrabutylammonium bromide (TBABr) based DES of different hydrogen bond donors (HBD), including ethylene glycol (EG), glycerol (Gly), 1,3-propanediol (1,3-PD) and 1,5-pentanediol (1,5-PD), to calf thymus DNA was investigated using fluorescence spectroscopy. It was found that the shorter the alkyl chain length (2 carbons) and higher EG ratios of TBABr:EG (1:5) increased the binding constant (Kb) between DES and DNA up to 5.75 × 105 kJ mol-1 and decreased the binding of Gibbs energy (ΔGo) to 32.86 kJ mol-1. Through displacement studies, all synthesised DESs have been shown to displace DAPI (4',6-diamidino-2-phenylindole) and were able to bind on the minor groove of Adenine-Thymine (AT)-rich DNA. A higher number of hydroxyl (OH) groups caused the TBABr:Gly to form more hydrogen bonds with DNA bases and had the highest ability to quench DAPI from DNA, with Stern-Volmer constants (Ksv) of 115.16 M-1. This study demonstrated that the synthesised DESs were strongly bound to DNA through a combination of electrostatic, hydrophobic, and groove binding. Hence, DES has the potential to solvate and stabilise nucleic acid structures.
  7. Fulltext Elucidating the Aromatic Properties of Covalent Organic Frameworks Surface for Enhanced Polar Solvent Adsorption
    Borzehandani MY, Abdulmalek E, Abdul Rahman MB, Latif MAM
    Polymers (Basel), 2021 Jun 03;13(11).
    PMID: 34205141 DOI: 10.3390/polym13111861
    Covalent organic frameworks (COFs) have a distinguished surface as they are mostly made by boron, carbon, nitrogen and oxygen. Many applications of COFs rely on polarity, size, charge, stability and hydrophobicity/hydrophilicity of their surface. In this study, two frequently used COFs sheets, COF-1 and covalent triazine-based frameworks (CTF-1), are studied. In addition, a theoretical porous graphene (TPG) was included for comparison purposes. The three solid sheets were investigated for aromaticity and stability using quantum mechanics calculations and their ability for water and ethanol adsorption using molecular dynamics simulations. COF-1 demonstrated the poorest aromatic character due to the highest energy delocalization interaction between B-O bonding orbital of sigma type and unfilled valence-shell nonbonding of boron. CTF-1 was identified as the least kinetically stable and the most chemically reactive. Both COF-1 and CTF-1 showed good surface properties for selective adsorption of water via hydrogen bonding and electrostatic interactions. Among the three sheets, TPG's surface was mostly affected by aromatic currents and localized π electrons on the phenyl rings which in turn made it the best platform for selective adsorption of ethanol via van der Waals interactions. These results can serve as guidelines for future studies on solvent adsorption for COFs materials.
  8. Fulltext Size-Controlled Preparation of Docetaxel- and Curcumin-Loaded Nanoemulsions for Potential Pulmonary Delivery
    Asmawi AA, Salim N, Abdulmalek E, Abdul Rahman MB
    Pharmaceutics, 2023 Feb 15;15(2).
    PMID: 36839974 DOI: 10.3390/pharmaceutics15020652
    Lung cancer is one of the deadliest pulmonary diseases in the world. Although docetaxel (DTX) has exhibited superior efficacy in lung cancer treatment, it has demonstrated numerous adverse effects and poor bioavailability. The natural product extract, curcumin (CCM), has reportedly reduced toxicity and synergistically improved DTX bioavailability. Nonetheless, the hydrophobic nature of DTX and CCM limits their clinical use. Nanoemulsion pulmonary delivery of DTX and CCM has demonstrated potential as a drug carrier to alleviate these drawbacks. The controlled preparation of inhalable DTX- and CCM-loaded nanoemulsions within the 100 to 200 nm range was explored in this study. A response surface methodology (RSM) based on a central composite design (CCD) was utilized to fabricate the desired size of the nanoemulsion under optimized conditions. Different process parameters were employed to control the size of the nanoemulsions procured through a high-energy emulsification technique. The size of the resultant nanoemulsions decreased with increasing energy input. The actual response according to the targeted sizes for DTX- and CCM-loaded nanoemulsion models exhibited excellent agreement with the predicted value at below 5% residual standard error under optimized conditions. The nanoemulsion of 100 nm particle size demonstrated better membrane permeability than their larger counterparts. Moreover, the formulations documented favorable physicochemical and aerodynamic pulmonary delivery properties and reduced toxicity in human lung fibroblast (MRC-5) cells. Hence, this tunable size of nanoemulsions could be a suitable alternative drug delivery for pulmonary diseases with increased local lung concentration.
  9. Fulltext Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design
    Asmawi AA, Salim N, Abdulmalek E, Abdul Rahman MB
    Int J Mol Sci, 2020 Jun 19;21(12).
    PMID: 32575390 DOI: 10.3390/ijms21124357
    The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.
  10. Fulltext Progress in Mesoporous Silica Nanoparticles as Drug Delivery Agents for Cancer Treatment
    Mohamed Isa ED, Ahmad H, Abdul Rahman MB, Gill MR
    Pharmaceutics, 2021 Jan 24;13(2).
    PMID: 33498885 DOI: 10.3390/pharmaceutics13020152
    Cancer treatment and therapy have made significant leaps and bounds in these past decades. However, there are still cases where surgical removal is impossible, metastases are challenging, and chemotherapy and radiotherapy pose severe side effects. Therefore, a need to find more effective and specific treatments still exists. One way is through the utilization of drug delivery agents (DDA) based on nanomaterials. In 2001, mesoporous silica nanoparticles (MSNs) were first used as DDA and have gained considerable attention in this field. The popularity of MSNs is due to their unique properties such as tunable particle and pore size, high surface area and pore volume, easy functionalization and surface modification, high stability and their capability to efficiently entrap cargo molecules. This review describes the latest advancement of MSNs as DDA for cancer treatment. We focus on the fabrication of MSNs, the challenges in DDA development and how MSNs address the problems through the development of smart DDA using MSNs. Besides that, MSNs have also been applied as a multifunctional DDA where they can serve in both the diagnostic and treatment of cancer. Overall, we argue MSNs provide a bright future for both the diagnosis and treatment of cancer.
  11. Fulltext Molecular dynamics simulation of palmitate ester self-assembly with diclofenac
    Abedi Karjiban R, Basri M, Abdul Rahman MB, Salleh AB
    Int J Mol Sci, 2012;13(8):9572-9583.
    PMID: 22949816 DOI: 10.3390/ijms13089572
    Palm oil-based esters (POEs) are unsaturated and non-ionic esters with a great potential to act as chemical penetration enhancers and drug carriers for transdermal drug nano-delivery. A ratio of palmitate ester and nonionic Tween80 with and without diclofenac acid was chosen from an experimentally determined phase diagram. Molecular dynamics simulations were performed for selected compositions over a period of 15 ns. Both micelles showed a prolate-like shape, while adding the drug produced a more compact micellar structure. Our results proposed that the drug could behave as a co-surfactant in our simulated model.
  12. Fulltext Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
    Wahgiman NA, Salim N, Abdul Rahman MB, Ashari SE
    Int J Nanomedicine, 2019;14:7323-7338.
    PMID: 31686809 DOI: 10.2147/IJN.S212635
    BACKGROUND: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.

    METHODS: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.

    RESULTS: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).

  13. Bioinformatics survey of the metal usage by psychrophilic yeast Glaciozyma antarctica PI12
    Foong PM, Abedi Karjiban R, Normi YM, Salleh AB, Abdul Rahman MB
    Metallomics, 2015 Jan;7(1):156-64.
    PMID: 25412156 DOI: 10.1039/c4mt00163j
    Metal ions are one of the essential elements which are extensively involved in many cellular activities. With rapid advancements in genome sequencing techniques, bioinformatics approaches have provided a promising way to extract functional information of a protein directly from its primary structure. Recent findings have suggested that the metal content of an organism can be predicted from its complete genome sequences. Characterizing the biological metal usage of cold-adapted organisms may help to outline a comprehensive understanding of the metal-partnerships between the psychrophile and its adjacent environment. The focus of this study is targeted towards the analysis of the metal composition of a psychrophilic yeast Glaciozyma antarctica PI12 isolated from sea ice of Antarctica. Since the cellular metal content of an organism is usually reflected in the expressed metal-binding proteins, the putative metal-binding sequences from G. antarctica PI12 were identified with respect to their sequence homologies, domain compositions, protein families and cellular distribution. Most of the analyses revealed that the proteome was enriched with zinc, and the content of metal decreased in the order of Zn > Fe > Mg > Mn, Ca > Cu. Upon comparison, it was found that the metal compositions among yeasts were almost identical. These observations suggested that G. antarctica PI12 could have inherited a conserved trend of metal usage similar to modern eukaryotes, despite its geographically isolated habitat.
  14. Fulltext Chemoenzymatic epoxidation of alkenes and reusability study of the phenylacetic acid
    Abdulmalek E, Arumugam M, Mizan HN, Abdul Rahman MB, Basri M, Salleh AB
    ScientificWorldJournal, 2014;2014:756418.
    PMID: 24587751 DOI: 10.1155/2014/756418
    Here, we focused on a simple enzymatic epoxidation of alkenes using lipase and phenylacetic acid. The immobilised Candida antarctica lipase B, Novozym 435 was used to catalyse the formation of peroxy acid instantly from hydrogen peroxide (H2O2) and phenylacetic acid. The peroxy phenylacetic acid generated was then utilised directly for in situ oxidation of alkenes. A variety of alkenes were oxidised with this system, resulting in 75-99% yield of the respective epoxides. On the other hand, the phenylacetic acid was recovered from the reaction media and reused for more epoxidation. Interestingly, the waste phenylacetic acid had the ability to be reused for epoxidation of the 1-nonene to 1-nonene oxide, giving an excellent yield of 90%.
  15. Various polar tripeptides as asymmetric organocatalyst in direct aldol reactions in aqueous media
    Bayat S, Tejo BA, Salleh AB, Abdmalek E, Normi YM, Abdul Rahman MB
    Chirality, 2013 Nov;25(11):726-34.
    PMID: 23966316 DOI: 10.1002/chir.22205
    A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio- and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media.
  16. Application of artificial neural network for yield prediction of lipase-catalyzed synthesis of dioctyl adipate
    Abdul Rahman MB, Chaibakhsh N, Basri M, Salleh AB, Abdul Rahman RN
    Appl Biochem Biotechnol, 2009 Sep;158(3):722-35.
    PMID: 19132557 DOI: 10.1007/s12010-008-8465-z
    In this study, an artificial neural network (ANN) trained by backpropagation algorithm, Levenberg-Marquadart, was applied to predict the yield of enzymatic synthesis of dioctyl adipate. Immobilized Candida antarctica lipase B was used as a biocatalyst for the reaction. Temperature, time, amount of enzyme, and substrate molar ratio were the four input variables. After evaluating various ANN configurations, the best network was composed of seven hidden nodes using a hyperbolic tangent sigmoid transfer function. The correlation coefficient (R2) and mean absolute error (MAE) values between the actual and predicted responses were determined as 0.9998 and 0.0966 for training set and 0.9241 and 1.9439 for validating dataset. A simulation test with a testing dataset showed that the MAE was low and R2 was close to 1. These results imply the good generalization of the developed model and its capability to predict the reaction yield. Comparison of the performance of radial basis network with the developed models showed that radial basis function was more accurate but its performance was poor when tested with unseen data. In further part of the study, the feedforward backpropagation model was used for prediction of the ester yield within the given range of the main parameters.
  17. Scale-up synthesis of lipase-catalyzed palm esters in stirred-tank reactor
    Keng PS, Basri M, Ariff AB, Abdul Rahman MB, Abdul Rahman RN, Salleh AB
    Bioresour Technol, 2008 Sep;99(14):6097-104.
    PMID: 18243690 DOI: 10.1016/j.biortech.2007.12.049
    Lipase-catalyzed production of palm esters by alcoholysis of palm oil with oleyl alcohol in n-hexane was performed in 2L stirred-tank reactor (STR). Investigation on the performance of reactor operation was carried out in batch mode STR with single impeller mounted on the centrally located shaft. Rushton turbine (RT) impellers provide the highest reaction yield (95.8%) at lower agitation speed as compared to AL-hydrofoil (AL-H) and 2-bladed elephant ear (EE) impellers. Homogenous enzyme particles suspension was obtained at 250 rpm by using RT impeller. At higher impeller speed, the shear effect on the enzyme particles caused by agitation has decreased the reaction performance. Palm esters reaction mixture in STR follows Newtons' law due to the linear relation between the shear stress (tau) and shear rate (dupsilon/dy). High stability of Lipozyme RM IM was observed as shown by its ability to be repeatedly used to give high percentage yield (79%) of palm esters even after 15 cycles of reaction. The process was successfully scale-up to 75 L STR (50 L working volume) based on a constant impeller tip speed approach, which gave the yield of 97.2% after 5h reaction time.
  18. Molecular dynamics study of the structure, flexibility and dynamics of thermostable l1 lipase at high temperatures
    Abedi Karjiban R, Abdul Rahman MB, Basri M, Salleh AB, Jacobs D, Abdul Wahab H
    Protein J, 2009 Jan;28(1):14-23.
    PMID: 19130194 DOI: 10.1007/s10930-008-9159-7
    Molecular Dynamics (MD) simulations have been used to understand how protein structure, dynamics, and flexibility are affected by adaptation to high temperature for several years. We report here the results of the high temperature MD simulations of Bacillus stearothermophilus L1 (L1 lipase). We found that the N-terminal moiety of the enzyme showed a high flexibility and dynamics during high temperature simulations which preceded and followed by clear structural changes in two specific regions; the small domain and the main catalytic domain or core domain of the enzyme. These two domains interact with each other through a Zn(2+)-binding coordination with Asp-61 and Asp-238 from the core domain and His-81 and His-87 from the small domain. Interestingly, the His-81 and His-87 were among the highly fluctuated and mobile residues at high temperatures. The results appear to suggest that tight interactions of Zn(2+)-binding coordination with specified residues became weak at high temperature which suggests the contribution of this region to the thermostability of the enzyme.
  19. Fulltext Imidazole-rich copper peptides as catalysts in xenobiotic degradation
    Begum SZ, Nizam NSM, Muhamad A, Saiman MI, Crouse KA, Abdul Rahman MB
    PLoS One, 2020;15(11):e0238147.
    PMID: 33147237 DOI: 10.1371/journal.pone.0238147
    Laccases, oxidative copper-enzymes found in fungi and bacteria were used as the basis in the design of nona- and tetrapeptides. Laccases are known to be excellent catalysts for the degradation of phenolic xenobiotic waste. However, since solvent extraction of laccases is environmentally-unfriendly and yields obtained are low, they are less preferred compared to synthetic catalysts. The histidine rich peptides were designed based on the active site of laccase extracted from Trametes versicolor through RCSB Protein Data Bank, LOMETS and PyMol software. The peptides were synthesized using Fmoc-solid phase peptide synthesis (SPPS) with 30-40% yield. These peptides were purified and characterized using LC-MS (purities >75%), FTIR and NMR spectroscopy. Synthesized copper(II)-peptides were crystallized and then analyzed spectroscopically. Their structures were elucidated using 1D and 2D NMR. Standards (o,m,p-cresol, 2,4-dichlorophenol) catalysed using laccase from Trametes versicolor (0.66 U/mg) were screened under different temperatures and stirring rate conditions. After optimizing the degradation of the standards with the best reaction conditions reported herein, medications with phenolic and aromatic structures such as ibuprofen, paracetamol (acetaminophen), salbutamol, erythromycin and insulin were screened using laccase (positive control), apo-peptides and copper-peptides. Their activities evaluated using GC-MS, were compared with those of peptide and copper-peptide catalysts. The tetrapeptide was found to have the higher degradation activity towards salbutamol (96.8%) compared with laccase at 42.8%. Ibuprofen (35.1%), salbutamol (52.9%) and erythromycin (49.7%) were reported to have the highest degradation activities using Cu-tetrapeptide as catalyst when compared with the other medications. Consequently, o-cresol (84%) was oxidized by Tp-Cu while the apo-peptides failed to oxidize the cresols. Copper(II)-peptides were observed to have higher catalytic activity compared to their parent peptides and the enzyme laccase for xenobiotic degradation.
  20. Fulltext Efficacy of Afatinib in the Treatment of Patients with Non-Small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
    Maarof NNN, Alsalahi A, Abdulmalek E, Fakurazi S, Tejo BA, Abdul Rahman MB
    Cancers (Basel), 2021 Feb 08;13(4).
    PMID: 33567737 DOI: 10.3390/cancers13040688
    Several randomized controlled trials (RCTs) evaluated the afatinib efficacy in patients with advanced non-small cell lung cancer (NSCLC) and recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This review systemically outlined and meta-analyzed the afatinib efficacy in NSCLC and R/M HNSCC in terms of overall survival (OS) and progression-free survival (PFS) endpoints. Records were retrieved from PubMed, Web of Science, and ScienceDirect from 2011 to 2020. Eight afatinib RCTs were included and assessed for the risk of bias. In meta-analysis, overall pooled effect size (ES) of OS in afatinib group (AG) significantly improved in all RCTs and NSCLC-RCTs [hazard ratios (HRs): 0.89 (95% CI: 0.81-0.98, p = 0.02); I2 = 0%, p = 0.71/ 0.86 (95% CI: 0.76-0.97; p = 0.02); I2 = 0%, p = 0.50, respectively]. ES of PFS in AG significantly improved in all RCTs, NSCLC-RCTs, and HNSCC-RCTs [HRs: 0.75 (95% CI: 0.68-0.83; p < 0.00001); I2 = 26%, p = 0.24; 0.75 (95% CI: 0.66-0.84; p < 0.00001); I2 = 47%, p = 0.15/0.76 (95% CI: 0.65-88; p = 0.0004); I2 = 34%, p = 0.0004, respectively]. From a clinical viewpoint of severity, interstitial lung disease, dyspnea, pneumonia, acute renal failure, and renal injury were rarely incident adverse events in the afatinib group. In conclusion, first- and second-line afatinib monotherapy improved the survival of patients with NSCLC, while second-line afatinib monotherapy could be promising for R/M HNSCC. The prospective protocol is in PROSPERO (ID = CRD42020204547).
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