Various blend ratios of high-density polyethylene (HDPE) and ultra high molecular weight polyethylene (UHMWPE) were prepared with the objective of determining their suitability as biomaterials. In the unfilled state, a blend of 50/50 (HDPE/UHMWPE) ratio by weight was found to yield optimum properties in terms of processability and mechanical properties. Hydroxyapatite (HA) was compounded with the optimum blend ratio. The effects of HA loading, varied from 0 to 50wt% for both filled and unfilled blends were tested for mechanical properties. It was found that the inclusion of HA in the blend led to a remarkable improvement of mechanical properties compared to the unfilled blend. In order to improve the bonding between the polymer blend and the filler, the HA used was chemically treated with a coupling agent known as 3-(trimethoxysiyl) propyl methacrylate and the treated HA was mixed into the blend. The effect of mixing the blend with silane-treated HA also led to an overall improvement of mechanical properties.
There is a great demand of Hydroxyapatite (HA) material in Orthopaedics and Dental applications due to its similarity to human bone. However, the lack of availability and due to high import cost of this material in Malaysia, research in producing synthetic HA locally is therefore timely. The use of local resources as the raw materials for the production of HA is also desirable in reducing the overall cost of HA. In this study, two HA materials were synthesised from different starting precursors, i.e. commercial pure Ca(OH)2 (HAS) and Ca(OH)2 directly from a local natural limestone deposit (HAL). Whereas a commercially available HA "Captal 60" (HAC) was used as reference. The synthesised powders obtained were fired at 1000 degrees C and at 1250 degrees C. Characterisation evaluations on bulk properties were carried out using XRD, SEM-EDX, ICP and FTIR. The results indicate that both HAS and HAL are comparable to HAC even at 1000 degrees C. Thus, the local natural limestone can be used to form HA. However, the overall appearance of these materials are quite different (HAC - blue, HAS - greenish and HAL - light green). The reasons for this and the subsequent mechanical and bioactive effects of these materials are currently being investigated.
The paper discusses the influence of sintering temperature on the microstructure and strength of hydroxyapatite ceramics prepared using the extrusion process. The average pore diameters observed were in the range of approximately 150mm to 300mm whereas the compaction strength was found to be around 120-160 MPa.
Hydroxyapatite, (HA; Ca1O(PO4)6(OH)2) has been successfully applied in medical and dental applications for several years due to its excellent biocompatibility. The usage of HA in Malaysia, however, is limited due to the lack of availability. Therefore the aim of this work is to produce HA materials from both pure chemicals and from Malaysian natural limestone precursors, and to compare their bulk properties. However, parts of Malaysian natural limestone deposits actually consist of a combination of Ca(OH)2 and CaCO3. In order to utilise the limestone to produce HA material, the combination of these commercially pure chemicals as HA precursors should still work. In order to test this hypothesis, two HAs were produced by wet synthesis technique utilising (a) combination of Ca(OH)2 + CaCO3 from pure commercial chemicals [WCC] and (b) a local natural limestone [WL] precursors. The HAs produced; WCC and WL, were compacted into discs and sintered at 1250 degrees C. The characterisations and evaluations conducted were XRD, SEM-EDX, FTIR and shrinkage factor. The results indicate that WL gives slightly better bulk properties compared to WCC.
The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities.
A new series of antioxidants, namely imines bearing the well-known free radical scavenger group 3,4,5-trimethoxybenzyloxy, was designed and synthesized. Theoretical calculations based on density functional theory (DFT) were performed to understand the antioxidant activities. Experimental studies evaluating the antioxidant activities of the compounds using DPPH and FRAP assays verified the predictions obtained by DMOL3 based on DFT.1. The DPPH radical scavenging activities depended on the substitution pattern of the aromatic aldehyde, with both the substitution type and position showing significant effects. Compounds 7b, 7c and 7d, which contain a phenolic hydroxyl group at the para position to the imine as well as, additional electron donating groups at the ortho-position to this hydroxyl group, exhibited IC₅₀ values of 62, 75 and 106 μg/mL, respectively, and potent antioxidant activities against DPPH, which were better than that of the reference compound BHT. With the exception of compounds 7a and 7h with a phenolic hydroxyl group at the ortho position, all of the investigated compounds exhibited ferric reducing activities above 1000 μM. Correlation analysis between the two antioxidant assays revealed moderate positive correlation (r = 0.59), indicating differing antioxidant activities based on the reaction mechanism. Therefore, imines bearing a 3,4,5-trimethoxybenzyloxy group can be proposed as potential antioxidants for tackling oxidative stress.
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.
Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5-trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide in the presence of KOH led to the corresponding 1,3,4-oxadiazole and various alkylated derivatives. The newly synthesized compounds were purified and the structures of the products were elucidated and confirmed on the basis of their analytical and spectral data. Their antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) and Ferric Reducing Antioxidant Power (FRAP) assays. The thiosemicarbazide derivatives were highly active in both antioxidant assays with the lowest IC50 value for DPPH radical scavenging. Theoretical calculations based on density functional theory (DFT) were performed to understand the relative importance of NH, SH and CH hydrogens on the radical scavenging activities of these compounds.
A library of novel 2,5-disubtituted-1,3,4-oxadiazoles with benzimidazole backbone (3a-3r) was synthesized and evaluated for their potential as β-glucuronidase inhibitors. Several compounds such as 3a-3d, 3e-3j, 3l-3o, 3q and 3r showed excellent inhibitory potentials much better than the standard (IC50=48.4±1.25μM: d-saccharic acid 1,4-lactone). All the synthesized compounds were characterized satisfactorily by using different spectroscopic methods. We further evaluated the interaction of the active compounds and the enzyme active site with the help of docking studies.
Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.
Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents. Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes.
Twenty five 4, 6-dichlorobenzimidazole derivatives (1-25) have been synthesized and evaluated against β-glucuronidase inhibitory activity. The compounds which actively inhibit β-glucuronidase activity have IC50 values ranging between 4.48 and 46.12 μM and showing better than standard d-saccharic acid 1,4 lactone (IC50=48.4 ± 1.25 μM). Molecular docking provided potential clues to identify interactions between the active molecules and the enzyme which further led us to identify plausible binding mode of all the benzimidazole derivatives. This study confirmed that presence of hydrophilic moieties is crucial to inhibit the human β-glucuronidase.
Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2±0.25 and 83.5±1.0μM when compared with the standard acarbose (IC50=840±1.73μM). Among the series compound 2 having IC50 value (18.3±0.56μM), 9 (83.5±1.0μM), 11 (3.3±0.25μM), 12 (2.2±0.25μM), 14 (11.8±0.15μM), and 20 (3.0±0.15μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking.
Hydroxyapatite (HAp) is an attractive bioceramics due to its similar composition to bone mineral and its ability to promote bone-implant interaction. However, its low strength has limited its application as load bearing implants. This paper presented a work focusing on the improvement of HAp mechanical property by synthesizing iron (Fe)-reinforced bovine HAp nanocomposite powders via mechanosynthesis method. The synthesis process was performed using high energy milling at varied milling time (3, 6, 9, and 12h). The samples were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM). Its mechanical properties were investigated by micro-Vicker's hardness and compression tests. Results showed that milling time directly influenced the characteristics of the nanocomposite powders. Amorphous BHAp was formed after 9 and 12h milling in the presence of HPO4(2-) ions. Continuous milling has improved the crystallinity of Fe without changing the HAp lattice structure. The nanocomposite powders were found in spherical shape, agglomerated and dense after longer milling time. The hardness and Young's modulus of the nanocomposites were also increased at 69% and 66%, respectively, as the milling time was prolonged from 3 to 12h. Therefore, the improvement of the mechanical properties of nanocomposite was attributed to high Fe crystallinity and homogenous, dense structure produced by mechanosynthesis.
Efficacy of eight recently developed and used anthelmintics of the benzimidazole carbamates; mebendazole, flubendazole, oxfendazole, albendazole, oxibendazole, 790163 proflubendazole, 780118 "cyanide" benzimidazole and 780120 "selenium" benzimidazole was tested orally against the enteral immature larval and adult stages of Trichinella spiralis in mice. Six of these derivatives of methyl benzimidazole-2-carbamates have an aryl and two have an alkyl substituent at the 5'-position of the parent benzimidazole ring. The nature of these substituents was found to be related to the antitrichinellous activity of the compounds. Compounds with the 5'-substituent linked to the parent benzimidazole ring by either a carbon, sulfur or an oxygen atom are more potent than those bridged by selenium or by the carbon with an attached-CN group. The result clearly indicates that the benzimidazoles are invariably more potent against immature enteral phase than the adult worms. This finding would be of importance in a targeted synthesis of new, effective derivatives of benzimidazole, e.g., in the screening for more important tissue-dwelling nematodes like filarial worms.
1. Substrate specificity of purified king cobra (Ophiophagus hannah) venom L-amino acid oxidase was investigated. 2. The enzyme was highly specific for the L-enantiomer of amino acid. Effective oxidation of L-amino acid by the enzyme requires the presence of a free primary alpha-amino group but the alpha-carboxylate group is not as critical for the catalysis. 3. The enzyme was very active against L-Lys, L-Phe, L-Leu, L-Tyr, L-Tryp, L-Arg, L-Met, L-ornithine, L-norleucine and L-norvaline and moderately active against L-His, L-cystine and L-Ileu. Other L-amino acids were oxidized slowly or not oxidized. 4. The data suggest the presence of a side chain binding site in the enzyme, and that the binding site comprises at least five 'subsites': the hydrophobic subsites a, b and c; and the two 'amino' binding subsites d and e. Subsite b appears to be able to accommodate two methylene/methyl carbons.
Gangliosides and glycophorin are receptors for wheat germ agglutinin. The competitive binding of these molecules to wheat germ agglutinin is studied by electron spin resonance spectroscopy with spin labels attached to the oligosaccharide chains of gangliosides. Evidence shows that glycophorin is more accessible to wheat germ agglutinin binding than gangliosides. The interactions of gangliosides and glycophorin in liposomes is disrupted on low level binding of WGA.