MyMedR

[Chemical studies on the analgesic indole alkaloids from the traditional medicine (Mitragyna speciosa) used for opium substitute]

Takayama H, Aimi N, Sakai S

Yakugaku Zasshi, 2000 Oct;120(10):959-67.

PMID: 11082707

The leaves of a tropical plant, Mitragyna speciosa Korth. (Rubiaceae), have been traditionally used as a substitute for opium. By phytochemical studies on the constituents of the plant growing in Thailand as well as in Malaysia, several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids including new natural products were isolated. The structures of these new compounds were elucidated by the modern spectroscopic methods and/or chiral-total syntheses. The chiral total synthesis of (-)-mitragynine, a major component of this plant, was achieved. Potent opioid agonistic properties of mitragynine, which acts on mu- and delta-opioid subtype receptors, and of mitragynine pseudoindoxyl, whose analgesic activity is more potent than that of morphine, were clarified in in vitro experiments. The essential structural features in mitragynine for revealing the analgesic activity were elucidated by pharmacological evaluation of the natural and synthetic mitragynine derivatives.

Matched MeSH terms: Structure-Activity Relationship

In vitro modulation of naturally occurring flavonoids on cytochrome P450 2A6 (CYP2A6) activity

Tiong KH, Yiap BC, Tan EL, Ismail R, Ong CE

Xenobiotica, 2010 Jul;40(7):458-66.

PMID: 20402563 DOI: 10.3109/00498251003786749

1. The effect of flavonoids on coumarin 7-hydroxylation, an activity marker of an important human liver cytochrome P450 isoform, cytochrome P450 2A6 (CYP2A6), was investigated in this study. 2. Coumarin 7-hydroxylase activity was measured fluorometrically in reaction mixtures containing cDNA-expressed CYP2A6, nicotinamide adenine dinucleotide phosphate generating system and 10 uM coumarin, at various concentrations of flavonoids. 3. Among the 23 compounds tested, most of the active members were from flavonol group of hydroxylated flavonoids, with myricetin being the most potent inhibitor followed by quercetin, galangin, and kaempferol. 4. Further exploration of the inhibition mechanism of these compounds revealed that myricetin, galangin, and kaempferol exhibited mixed-type of inhibition pattern while quercetin was observed to exhibit competitive mode of inhibition. 5. Structure-function analyses revealed that degree of inhibition was closely related to the number and location of hydroxyl groups, glycosylation of the free hydroxyl groups, degree of saturation of the flavane nucleus as well as the presence of the alkoxylated function.

Matched MeSH terms: Structure-Activity Relationship

QSPR prediction of the hydroxyl radical rate constant of water contaminants

Borhani TN, Saniedanesh M, Bagheri M, Lim JS

Water Res, 2016 07 01;98:344-53.

PMID: 27124124 DOI: 10.1016/j.watres.2016.04.038

In advanced oxidation processes (AOPs), the aqueous hydroxyl radical (HO) acts as a strong oxidant to react with organic contaminants. The hydroxyl radical rate constant (kHO) is important for evaluating and modelling of the AOPs. In this study, quantitative structure-property relationship (QSPR) method is applied to model the hydroxyl radical rate constant for a diverse dataset of 457 water contaminants from 27 various chemical classes. The constricted binary particle swarm optimization and multiple-linear regression (BPSO-MLR) are used to obtain the best model with eight theoretical descriptors. An optimized feed forward neural network (FFNN) is developed to investigate the complex performance of the selected molecular parameters with kHO. Although the FFNN prediction results are more accurate than those obtained using BPSO-MLR, the application of the latter is much more convenient. Various internal and external validation techniques indicate that the obtained models could predict the logarithmic hydroxyl radical rate constants of a large number of water contaminants with less than 4% absolute relative error. Finally, the above-mentioned proposed models are compared to those reported earlier and the structural factors contributing to the AOP degradation efficiency are discussed.

Matched MeSH terms: Quantitative Structure-Activity Relationship*

Fulltext Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Anasir MI, Ramanathan B, Poh CL

Viruses, 2020 03 26;12(4).

PMID: 32225021 DOI: 10.3390/v12040367

Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

Matched MeSH terms: Structure-Activity Relationship

Fulltext QSAR Studies on Neuraminidase Inhibitors as Anti-influenza Agents

Veerasamy R, Rajak H

Turk J Pharm Sci, 2021 04 20;18(2):151-156.

PMID: 33900700 DOI: 10.4274/tjps.galenos.2020.45556

Objectives: The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for neuraminidase inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anti-influenza activity.

Materials and Methods: We have developed and validated 2D and 3D QSAR models by using multiple linear regression, partial least square regression, and k-nearest neighbor-molecular field analysis methods.

Results: 2D QSAR models had q2: 0.950 and pred_r2: 0.877 and 3D QSAR models had q2: 0.899 and pred_r2: 0.957. These results showed that the models werere predictive.

Conclusion: Parameters such as hydrogen count and hydrophilicity were involved in 2D QSAR models. The 3D QSAR study revealed that steric and hydrophobic descriptors were negatively contributed to neuraminidase inhibitory activity. The results of this study could be used as platform for design of better anti-influenza drugs.

Matched MeSH terms: Quantitative Structure-Activity Relationship

Fulltext Cytotoxic activities of chemical constituents from Mesua daphnifolia

Ee GC, Lim CK, Rahmat A, Lee HL

Trop Biomed, 2005 Dec;22(2):99-102.

PMID: 16883274

Detail chemical investigations on the stem bark of Mesua daphnifolia gave three triterpenoids and four xanthones. They are friedelin (1), friedelan-1,3-dione (2), lup-20(29)- en-3ss-ol (3), cudraxanthone G (4), ananixanthone (5), 1,3,5-trihydroxy-4-methoxyxanthone (6) and euxanthone (7). These chemical constituents were tested in vitro for their cytotoxic activities against four cell lines, MDA-MB-231 (human estrogen receptor negative breast cancer), HeLa (cervical carcinoma), CEM-SS (T-lymphoblastic leukemia) and CaOV3 (human ovarian cancer). Compound 4 showed a broad spectrum of activity against the MDA-MB-231, HeLa and CEM-SS cell lines with IC5 0 values of 1.3, 4.0 and 6.7 microg/ml respectively. Meanwhile, the other compounds 1, 2, 3, 5, 6 and 7 gave only selective activities against the cell lines.

Matched MeSH terms: Structure-Activity Relationship

Fulltext Ligand-based virtual screening using Bayesian inference network and reweighted fragments

Ahmed A, Abdo A, Salim N

ScientificWorldJournal, 2012;2012:410914.

PMID: 22623895 DOI: 10.1100/2012/410914

Many of the similarity-based virtual screening approaches assume that molecular fragments that are not related to the biological activity carry the same weight as the important ones. This was the reason that led to the use of Bayesian networks as an alternative to existing tools for similarity-based virtual screening. In our recent work, the retrieval performance of the Bayesian inference network (BIN) was observed to improve significantly when molecular fragments were reweighted using the relevance feedback information. In this paper, a set of active reference structures were used to reweight the fragments in the reference structure. In this approach, higher weights were assigned to those fragments that occur more frequently in the set of active reference structures while others were penalized. Simulated virtual screening experiments with MDL Drug Data Report datasets showed that the proposed approach significantly improved the retrieval effectiveness of ligand-based virtual screening, especially when the active molecules being sought had a high degree of structural heterogeneity.

Matched MeSH terms: Quantitative Structure-Activity Relationship*

Fulltext Comparative susceptibility of Periplaneta americana (L) to five pyrethroid insecticides

Vythilingam I, Sutivigit Y

Southeast Asian J. Trop. Med. Public Health, 1994 Sep;25(3):528-31.

PMID: 7777920

Five pyrethroids namely, lambda-cyhalothrin, permethrin, deltamethrin, cyfluthrin and alpha-cypermethrin were evaluated using adult male and female cockroaches, Periplaneta americana (L). The American cockroaches were exposed for 10 minutes to glass jars treated with different concentrations of the five pyrethroids. The cockroaches were susceptible to all five pyrethroids and the susceptibility based on LC50 and LC50 were observed to be in the following order: lambda-cyhalothrin > permethrin > deltamethrin > cyfluthrin > alpha-cypermethrin The results showed that lambda-cyhalothrin was the most effective and alpha-cypermethrin was the least effective against Periplaneta americana (L).

Matched MeSH terms: Structure-Activity Relationship

Hydroxapatite and tricalcium phosphate prepared by precipitation method

Cik Rohaida CH, Idris B, Mohd Reusmaazran Y, Rusnah M, Fadzley Izwan AM

Med J Malaysia, 2004 May;59 Suppl B:156-7.

PMID: 15468865

A mixture with different compositions of HA and TCP were synthesize in this work by precipitation method using Ca(NO3)2 4H2 and (NH4)2HPO4 as the starting materials. A mixture with HA and TCP phases in different ratios were produced. The powders were sintered from 1000 degrees C to 1250 degrees C. The phase compositions of the mixtures were then studied via XRD. This work shows that the pH value determines the different phase compositions of the HA-TCP mixture. Chemical analyses were carried out by FTIR. The microstructure was observed under SEM.

Matched MeSH terms: Structure-Activity Relationship

Effect of differences in physical and chemical properties of chitosan on endothelial cell adhesion and growth

Mai-Ngam K, Seetapan N, Sagnella S

Med J Malaysia, 2004 May;59 Suppl B:172-3.

PMID: 15468873

Matched MeSH terms: Structure-Activity Relationship

A "healthy apatite" for bone repair

Best SM, Patel N, Porter AE, Bonfield W

Med J Malaysia, 2004 May;59 Suppl B:129-30.

PMID: 15468852

Bone is unique in its ability to adapt structure to functional requirements, but as is all too obvious in an ever-ageing population it is susceptible to a number of degenerative diseases. Therefore there is an increasing need for materials for bone replacement. Clearly, the ideal material with which to replace bone, would be bone itself, but the major problem now facing us is that there is an insufficient supply of the natural bone to satisfy the clinical requirements. Hence, there is a need for the development of chemically synthesised bone graft substitutes

Matched MeSH terms: Structure-Activity Relationship

Calcium phosphate bone substitutes

Ginebra MP, Aparicio C, Engel E, Navarro M, Javier Gil F, Planell JA

Med J Malaysia, 2004 May;59 Suppl B:65-6.

PMID: 15468821

Matched MeSH terms: Structure-Activity Relationship

Preparation of naltrexone hydrochloride loaded poly (DL-lactide-co-glycolide) microspheres and the effect of polyvinyl alcohol (PVA) as surfactant on the characteristics of the microspheres

Suhaida MG, Yahya IB, Darmawati MY

Med J Malaysia, 2004 May;59 Suppl B:63-4.

PMID: 15468820

The aim of this study was to investigate the effect of the surfactant properties of polyvinyl alcohol (PVA) in enhancing the yield of small size microspheres. Naltrexone microspheres were prepared by solvent-solvent extraction evaporation process. PVA of various concentrations were added into the aqueous phase prior to the mixing process. The addition of PVA was expected to influence the shape, size distribution, drug loading and drug release profile. The results indicated that it is desirable to increase the weight fraction of the microspheres with size range below 106 mm for the highest possible yield.

Matched MeSH terms: Structure-Activity Relationship

Mechanical properties of HDPE/UHMWPE blends: effect of filler loading and filler treatment

Lai KL, Roziyanna A, Ogunniyi DS, Zainal AM, Azlan AA

Med J Malaysia, 2004 May;59 Suppl B:61-2.

PMID: 15468819

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.

Matched MeSH terms: Structure-Activity Relationship

Comparison of hydroxyapatite powders derived from different resources

Hee SL, Nik Intan NI, Fazan F

Med J Malaysia, 2004 May;59 Suppl B:77-8.

PMID: 15468827

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.

Matched MeSH terms: Structure-Activity Relationship

Biomimetic structures for implants and tissue engineering scaffolds

Ambrosio L, Battista S, Borzacchiello A, Borselli C, Causa F, De Santis R, et al.

Med J Malaysia, 2004 May;59 Suppl B:71-2.

PMID: 15468824

Matched MeSH terms: Structure-Activity Relationship

Microstructure and strength of extruded porous HA ceramics

Rusnah M, Andanastuti M, Idris B

Med J Malaysia, 2004 May;59 Suppl B:83-4.

PMID: 15468830

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.

Matched MeSH terms: Structure-Activity Relationship

Comparative study of synthesised hyroxyapatite from pure chemicals and Malaysian natural limestone precursors

Abu Bakar SH, Hussein Z, Hee SL, Fazan F

Med J Malaysia, 2004 May;59 Suppl B:81-2.

PMID: 15468829

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.

Matched MeSH terms: Structure-Activity Relationship

Lactic acid-based bioresorbable polymers: properties and traps

Vert M

Med J Malaysia, 2004 May;59 Suppl B:73-4.

PMID: 15468825

Matched MeSH terms: Structure-Activity Relationship

3,5-dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells

Roslie H, Chan KM, Rajab NF, Velu SS, Kadir SA, Bunyamin I, et al.

J Toxicol Sci, 2012 Feb;37(1):13-21.

PMID: 22293408

A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC(50)s of 78 µM, 38 µM, 67 µM and 19.5 µM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.

Matched MeSH terms: Structure-Activity Relationship

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