Institution
Gadjah Mada University
Education•Yogyakarta, Indonesia•
About: Gadjah Mada University is a education organization based out in Yogyakarta, Indonesia. It is known for research contribution in the topics: Population & Adsorption. The organization has 17307 authors who have published 21389 publications receiving 116561 citations. The organization is also known as: University of Gajah Mada & Universitas Gadjah Mada.
Topics: Population, Adsorption, Tourism, Government, Catalysis
Papers published on a yearly basis
Papers
More filters
••
TL;DR: In this paper, the radial distribution of quinones (tectoquinone, lapachol, desoxylapachol and its isomer) and other components in the ethanol-benzene (1:2) extract were measured by means of gas chromatography.
Abstract: Keywords: Tectona grandis / extractives / tectoquinone / desoxylapachol / tree age Abstract • Quinones are primarily responsible for the natural durability of teak. • The previous paper in this series reported on the natural termite resistance of teak trees of different ages (8-, 30- and 51-year-old trees). In this study, the radial distribution of quinones (tectoquinone, lapachol, desoxylapachol and its isomer) and other components in the ethanol-benzene (1:2) extract were measured by means of gas chromatography. • Significant differences in desoxylapachol or its isomer content were found among the outer heart- wood of 8-, 30- and 51-year old trees, as well as between the inner and outer parts of the heartwood. • All toxic quinone contents were positively correlated with the total extractive content. The highest correlation degree was measured in the isodesoxylapachol content. • Although linearly related, only modest correlations were observed between the natural termite re- sistance parameters and the content of tectoquinone and isodesoxylapachol. Mots-cles : Tectona grandis / extractibles / tectoquinone / desoxylapachol / âge des arbres
52 citations
••
TL;DR: Aaptamine was evaluated for its ability to bind to DNA to validate DNA binding as the primary mechanism of cytotoxicity and its derivatives’ whole cell and viral assay results are discussed.
Abstract: Aaptamine (1; Figure 1) is commonly isolated in large yields from various species of the marine sponge genus Aaptos (Order Hadromerida: Family Suberitidae)a, along with a handful of related compounds such as isoaaptamine (2) which contain the benzonapthyridine core structure (1–7). The isolation of aaptamine from the taxonomically unrelated species Luffariella (Order Dictyoceratida: Family Thorectidae) (3), Hymeniacidon (Order Halichondrida: Family Halichondriidae) (6), and Xestospongia (7) (Order Haplosclerida: Family Petrosiidae)b, indicates the likelihood of production of aaptamine from a microbial source. In fact, several novel metabolites containing the aaptamine core have come from one particular sponge (7), underlining likely contributions of the microbial community associated with the producer of aaptamine. A number of total synthetic studies have been published along with a limited collection of semi-synthetic derivatives since its original discovery (8–16). Considering its low molecular weight, aaptamine is relatively difficult to synthesize from available starting materials. Attempts to complete the unique fused tricycle have been made through quinoline and isoquinoline precursors, the best overall yield being 13 percent over 14 steps. Although the synthetic yield is low, it is likely to be the more cost efficient choice for the production of aaptamine, unless a microbial producer is found.
Figure 1
Structures of major aaptamine related marine natural products.
The proposed biogenesis of aaptamine suggests a possible Pictet-Spengler type condensation commonly attributed to many other natural alkaloids (16). Likewise, three common pharmacophores can be recognized in the aaptamine scaffold: isoquinoline, the largest class of alkaloids isolated from medicinal plants; dopamine, a compound affecting the central nervous system and behavior; and finally, quinoline, known primarily for its anti-malarial properties.
Aaptamine's potential for drug development is further evidenced by the actual results of a highly diverse group of molecular targets already evaluated. In addition to antiviral (5,17) and anticancer (4,6,18) activities, the aaptamines have a strong in vitro radical scavenging capacity (19) and have been shown to block α-adrenoceptor action (1) as well as inhibit α-1,3-glucanase (20) and monoamine oxidase (21). Still, compounds which are active against a variety of targets are certain to encounter problems with indiscriminant toxicities. It is important to recognize toxicity as a hurdle for the development of aaptamine as a useful drug but not let it prohibit the evaluation of its derivatives for therapeutic potential. The ‘privileged structures’ approach (22) is dependent on exploiting a scaffold's common mechanism of drug-target interaction for multiple targets. In a similar fashion, a key for the development of the aaptamine scaffold is the identification of its common mechanism of drug-target interaction.
Although it is difficult to determine if broad-spectrum DNA-interaction is a compound's definitive mechanism of cytotoxicity, it is clear that DNA interaction has a measurable influence on the mechanism. Small molecules that bind to DNA do not necessarily interact in the same way, in fact, there are several modes by which a ligand can bind and affect the structure and function of this substrate (23). Of these modes, intercalation is most prevalent with planar polycyclic aromatic systems like the aaptamines which insert between adjacent base-pairs of intact DNA, depending primarily on p-bond interactions and sometimes stacking several molecules together in the same area between base pairs.
The quinoline portion found in aaptamine's tri-cyclic core has already been the focus of SAR studies with derivatives of acridine (24), a structure that resembles aaptamine and is a well studied anti-cancer pharmacophore that intercalates DNA. The observed DNA binding activity of aaptamine may serve to explain some aspects of the compound's mechanism of activity against whole cell and viral pathogens.
Considering the high availability of the natural material and the remarkably broad activity displayed, this heterocyclic small molecule has excellent potential as a scaffold from which numerous derivatives can be made in an attempt to improve selectivity and pharmacokinetics.
Based on the synthetic work already published by Shen et al. (18), Hibino et al. (12), Pettit et al. (25,26) and Gul et al. (27) a preliminary SAR has been developed for the aaptamine scaffold in regard to cytotoxicity, antiviral and antimicrobial activity. Table 1 summarizes what has been learned of this relationship from the synthetic and natural derivatives of aaptamine.
Table 1
Summary of reported relative structure activity relationships for aaptamine based on general improvements of either potency or selectivity
Utilizing the information from this SAR, a semi-synthetic series of N-alkyl aaptamine derivatives was produced to complement previously published N-alkylation efforts that improved activity, and to investigate the effects of increasing the lipophilic character of the pharmacophore. In addition, it was proposed that selective demethylation of the C-9 hydroxyl would significantly increase the potency of the first generation N-alkyl derivatives. Our speculation was based on the evidence wherein 2 consistently demonstrated higher potency than 1 in a variety of biological assays; likewise the selective demethylation of the aaptamine derivatives would produce isoaaptamine analogs with higher potency. Two smaller groups of analogs were specifically produced to investigate the effect of dimerization on biological activity and the pro-drug behavior of sulfonyl esters relative to those previously studied.
52 citations
••
TL;DR: Anterior cruciate ligament reconstruction with peroneus longus autografts produces a functional score comparable to that of hamstring autografteds at a 1-year follow-up, with the advantages of larger graft diameter, less thigh hypotrophy and excellent ankle function based on AOFAS and FADI scores.
Abstract: A peroneus longus tendon autograft is used in many orthopaedic procedures and it is biomechanically comparable to a hamstring tendon autograft. Despite its potential, there are few studies that have evaluated the use of the peroneus longus tendon in ACL reconstruction. The aim of this study was to compare the clinical outcome and donor site morbidity of ACL reconstruction with hamstring tendon autografts versus peroneus longus tendon autografts in patients with an isolated ACL injury. Patients who underwent isolated single-bundle ACL reconstruction were allocated to two groups (hamstring and peroneus longus) and observed prospectively. Graft diameter was measured intraoperatively. Functional scores (IKDC, modified Cincinnati and Lysholm scores) were recorded preoperatively and 1 year after surgery. Donor site morbidities were assessed with thigh circumference measurements and ankle scoring with the AOFAS and FADI. Fifty-two patients (hamstring n = 28, peroneus n = 24) met the inclusion criteria. The peroneus longus graft diameter (8.8 ± 0.7 mm) was significantly larger than the hamstring diameter (8.2 ± 0.8 mm) (p = 0.012). There were no significant differences between the pre- and 1-year postoperative score between the hamstring and peroneus longus groups in the IKDC (n.s), modified Cincinnati (n.s), and Lysholm (n.s). The mean for the AOFAS was 97.3 ± 4.2 and for the FADI 98 ± 3.4 in the peroneus longus group, with a significant decrease in thigh circumference in the hamstring group (p = 0.002). Anterior cruciate ligament reconstruction with peroneus longus autografts produces a functional score (IKDC, modified Cincinnati, Lysholm) comparable to that of hamstring autografts at a 1-year follow-up, with the advantages of larger graft diameter, less thigh hypotrophy and excellent ankle function based on AOFAS and FADI scores. Prospective cohort study, Level II.
52 citations
••
TL;DR: The transformed intact protocorms, which are young orchid seedlings of P. amabilis, regenerated plants under the same conditions that showed the highest frequency of shooting, indicating that a kanamycin resistance gene under the control of the 35S promoter can be used as a selective marker.
Abstract: Phalaenopsis hybrids constitute a major ornamental crop. An important parent species for many of these hybrids is Phalaenopsis amabilis. We developed a convenient method for the genetic modification of P. amabilis using Agrobacterium tumefaciens. The transformed intact protocorms, which are young orchid seedlings of P. amabilis, regenerated plants under the same conditions that showed the highest frequency of shooting. A kanamycin resistance gene under the control of the 35S promoter can be used as a selective marker. In addition, T-DNA vectors containing the Arabidopsis class 1 KNOX gene, BP/KNAT1, were successfully introduced into protocorms. Shoots were generated with an abnormal leaf shape that was easily distinguished from that of normal shoots, indicating that BP/KNAT1 can be used as a visible marker gene. Furthermore, the protocorms transformed with BP/KNAT1 produced multiple shoots. Both the presence and expression of the transgene in transformed plants were confirmed by molecular analysis.
52 citations
••
TL;DR: A new scheme, multiple-layer embedding based on difference expansion of quad, is proposed, focusing on increasing capacity and visual quality of data hiding by reducing difference value in pixel with improved reduced difference expansion (IRDE).
52 citations
Authors
Showing all 17450 results
Name | H-index | Papers | Citations |
---|---|---|---|
Bunsho Ohtani | 71 | 371 | 19052 |
Lawrence H. Moulton | 71 | 266 | 20663 |
John M. Nicholls | 66 | 231 | 19014 |
Paul Meredith | 59 | 308 | 15489 |
Bernd M. Rode | 52 | 441 | 11367 |
Jan-Willem C. Alffenaar | 43 | 294 | 6378 |
Bernd Lehmann | 41 | 218 | 6027 |
Nawi Ng | 39 | 152 | 4470 |
Jean-Philippe Gastellu-Etchegorry | 38 | 192 | 4860 |
Mohd Hamdi | 38 | 190 | 5846 |
Keiko Sasaki | 36 | 319 | 5341 |
Jos G. W. Kosterink | 36 | 167 | 5132 |
A. C. Hayward | 34 | 106 | 6538 |
Eileen S. Scott | 33 | 177 | 3187 |
Michael R. Dove | 33 | 142 | 4334 |