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PubMed1990

Determination of hopanoid levels in bacteria using high-performance liquid chromatography.

A reverse-phase HPLC method to detect and quantify levels of hopanoids in bacteria has been developed. Chromophores have been introduced by derivatization and the levels of the C35 hopanoids and their conjugates can be measured in bacterial lipid extracts down to picomole levels. Some structural variations of the complex lipids were detected after derivatization and were easily purified using the same HPLC system. Zymomonas mobilis and Rhodospirillum rubrum extracts were examined using this system and different structural examples of the lipids were detected. The relative levels of the different triterpenes were very dependent on the growth conditions.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Spatial patterns of child growth in Papua New Guinea and their relation to environment, diet, socio-economic status and subsistence activities.

Anthropometric data from the 1982/83 Papua New Guinea (PNG) National Nutrition Survey were analysed to identify geographical patterns of child growth and investigate their relation to a wide range of environmental, dietary and socio-economic variables. Standardized growth scores for length-for-age (LAZ), weight-for-age (WAZ) and weight-for-length (WLZ) were calculated based on an internal PNG growth reference. Hierarchical Bayesian spatial models based on conditional autoregressive (CAR) priors were subsequently used to model spatial patterns in scores and their relation to different sets of covariates. The geographical differences were bigger for linear growth than for increases in weight. Growth was most reduced in parts of Milne Bay Province, Madang Province, the Torricelli/Prinz Alexander Ranges, and in the area occupied by Angan people. Socio-economic status was the most important factor determining variation in growth within populations. Differences in diet and, to a lesser extent, the physical environment were the main determining factor of differences among populations. Covariate adjustment accounted for more spatially structured variation in LAZ and WAZ than in WLZ. All variables indicating higher socio-economic status were correlated with better growth, as was a high consumption of imported and local high quality foods such as cereals, legumes, tinned fish/meat or fresh fish. This indicates that nutritional interventions in PNG should aim at promoting the consumption of such high energy and high protein foods as well as strengthening the general economic base of rural populations.

Analysis of Variance↗
PubMed1989

Somnogenic activity of O-acetylated and dimeric muramyl peptides.

Slow-wave sleep-promoting factors in brain and urine were identified as muramyl peptides (MPs), the building blocks of bacterial cell wall peptidoglycan. In this study, structural variations of MPs that occur naturally in bacterial peptidoglycan were investigated for somnogenic activity. Monomeric and dimeric MPs were isolated and purified from Neisseria gonorrhoeae and Actinomadura sp. strain R39. The structures of these MPs were verified by fast atom bombardment mass spectroscopy and tandem mass spectroscopy. After intracerebroventricular administration of MPs, electroencephalograms and brain temperatures of rabbits were recorded for 6 h and were analyzed to determine durations of slow-wave sleep, rapid-eye-movement sleep, and wakefulness. The 6-O acetylation of muramic acid enhanced the somnogenic effects of certain monomeric MPs relative to their non-O-acetylated (but otherwise identical) counterparts. Two monomeric MPs containing an unsubstituted amide (i.e., Iso-Gln) were inactive, thus confirming previous results showing that amidation of a variety of MPs can block somnogenic activity. Two peptide-cross-linked MP dimers tested had no effect on slow-wave sleep, although a third peptide-cross-linked MP containing a 1,6-anhydro muramyl end on one of its monomeric subunits, a structure that enhances somnogenic potency of un-cross-linked monomers, was somnogenic. Two dimers connected by glycosidic bonds and containing an Iso-Gln moiety were inactive. Two other glycosidically linked dimers that also contained an Iso-Gln moiety, but were of lower molecular weight, were somnogenic. In summary, 6-O acetylation of muramic acid in somnogenic MPs enhances activity, and as a class, peptide-linked dimeric MPs tend to be less active than their constituent monomers.

Acetylation↗
PubMed1986

Technology as an occasion for structuring: evidence from observations of CT scanners and the social order of radiology departments.

New medical imaging devices, such as the CT scanner, have begun to challenge traditional role relations among radiologists and radiological technologists. Under some conditions, these technologies may actually alter the organizational and occupational structure of radiological work. However, current theories of technology and organizational form are insensitive to the potential number of structural variations implicit in role-based change. This paper expands recent sociological thought on the link between institution and action to outline a theory of how technology might occasion different organizational structures by altering institutionalized roles and patterns of interaction. In so doing, technology is treated as a social rather than a physical object, and structure is conceptualized as a process rather than an entity. The implications of the theory are illustrated by showing how identical CT scanners occasioned similar structuring processes in two radiology departments and yet led to divergent forms of organization. The data suggest that to understand how technologies alter organizational structures researchers may need to integrate the study of social action and the study of social form.

Communication↗
PubMed1985

"Endogenous ligands" of benzodiazepine receptors, their structural analogs. Development of new psychotropic drugs.

This paper presents a review of literature data and results from investigations designed to determine the relation between structure, affinity to benzodiazepine receptors and pharmacological activity of possible endogenous ligands of benzodiazepine receptors and their electronic structural analogs. Structural variations of endogenous ligands of benzodiazepine receptors are substantiated to manifest themselves as active psychotropic drugs. On the basis of these considerations and experimental data, compounds with psychotropic activity and electronic structure, resembling that of "endogenous ligands" of benzodiazepine receptors, were developed.

Animals↗
PubMed1985

Isolation and characterization of an anti-peptide monoclonal antibody to human erythropoietin.

A site-specific monoclonal antibody to human erythropoietin has been developed. It is secreted by a hybridoma cell line derived from the fusion of murine myeloma cells with the splenocytes of a mouse that had been immunized with a 26-residue synthetic peptide antigen homologous to the amino-terminal sequence of the hormone. The antibody binds specifically to peptide, 125I-erythropoietin, and biologically active erythropoietin. The equilibrium dissociation constants of the antibody-erythropoietin and the antibody-peptide interactions are identical, Kd = 6.7 X 10(-9) M, suggesting strong conformational similarity or identity of the epitope as expressed on the peptide and the hormone. Immune complexes formed between the antibody and either human or rat erythropoietin exhibit full biologic activity. However, the antibody does not recognize the baboon, sheep, or canine hormones, indicating antigenic differences or structural variation among these erythropoietins. These results indicate that the amino-terminal region of erythropoietin is not involved in receptor binding. Furthermore, they form a basis for the study of the structure and function of the hormone using anti-peptide antibodies.

Animals↗
PubMed1987

Correlation of rhythmic variations in subcellular structures of rat hepatocytes, pancreatic acinar cells, and islet B cells.

Correlation of variations in subcellular structures of hepatocytes, pancreatic acinar cells, and islet B cells was examined morphometrically at six time points during 24 hr, using 24 Wistar male rats housed under standardized conditions (LD 12:12; light from 0600 to 1800). The morphometric features examined were subject to strong variations during the 24-hr period. The volume and surface densities of rough endoplasmic reticulum in hepatocytes and acinar cells were highest at 0400, when those of secretory granules in B cells were lowest. At 0400, the surface density of the plasma membranes of B cells facing the intercellular spaces exhibited its highest value. The volume density of glycogen granules in hepatocytes was highest 4 hr after the secretory granules of B cells showed the lowest value. The volume density of glycogen granules in hepatocytes decreased during the light cycle, being lowest at 2000, while that of secretory granules in acinar cells increased during the light cycle, being highest at 1600. At 1600 and 2000, the volume and surface densities of secretory granules were high in B cells. These results suggest that insulin secreted from B cells stimulates protein synthesis in hepatocytes and pancreatic acinar cells, but not directly the synthesis of glycogen granules and secretion of zymogen granules.

Animals↗
PubMed1991

Streptonigrin and related compounds. 5. Synthesis and evaluation of some isoquinoline analogues.

A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were prepared. The various quinones were evaluated for antimicrobial activity against Bacillus subtilis and root-growth inhibitory activity against Lepidium sativum. The effect of specific structural changes on these activities was examined with streptonigrin for comparison. The necessity of an aminoquinone function for activity is confirmed. With regard to the antibacterial activity, the isoquinoline analogues appear to be less active compared to the quinoline derivatives. However, the higher degree of antibacterial activity of the 1-benzylisoquinolines and the 1-nitrophenylisoquinolines compared to the 1-phenyl isoquinolines is noteworthy. In contrast to the results seen with the antibacterial activity, most of the isoquinoline analogues showed activity comparable to, or even higher than, that of streptonigrin in the root-growth inhibition assay. The 1-nitrophenylisoquinolines again appear to be the most active. The equal or greater potency of the benzyl analogue in comparison with the phenyl analogue was unexpected and questions the need for the extended conjugation and the geometry required for metal binding as considered earlier. It also opens up new possibilities for structural variation.

Anti-Bacterial Agents↗
PubMed2003

Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution.

GNRA tetraloops (N is A, C, G, or U; R is A or G) are basic building blocks of RNA structure that often interact with proteins or other RNA structural elements. Understanding sequence-dependent structural variation among different GNRA tetraloops is an important step toward elucidating the molecular basis of specific GNRA tetraloop recognition by proteins and RNAs. Details of the geometry and hydration of this motif have been based on high-resolution crystallographic structures of the GRRA subset of tetraloops; less is known about the GYRA subset (Y is C or U). We report here the structure of a GUAA tetraloop determined to 1.4 A resolution to better define these details and any distinctive features of GYRA tetraloops. The tetraloop is part of a 27-nt structure that mimics the universal sarcin/ricin loop from Escherichia coli 23S ribosomal RNA in which a GUAA tetraloop replaces the conserved GAGA tetraloop. The adenosines of the GUAA tetraloop form an intermolecular contact that is a commonplace RNA tertiary interaction called an A-minor motif. This is the first structure to reveal in great detail the geometry and hydration of a GUAA tetraloop and an A-minor motif. Comparison of tetraloop structures shows a common backbone geometry for each of the eight possible tetraloop sequences and suggests a common hydration. After backbone atom superposition, equivalent bases from different tetraloops unexpectedly depart from coplanarity by as much as 48 degrees. This variation displaces the functional groups of tetraloops implicated in protein and RNA binding, providing a recognition feature.

Crystallography, X-Ray↗
PubMed1998

Different forms of the mRNA encoding the heat-shock transcription factor are expressed during the life cycle of the parasitic helminth Schistosoma mansoni.

Several cDNAs and a gene encoding the heat-shock transcription factor (HSF) of schistosome were cloned, and multiple forms of the mRNA were found at different developmental stages of the parasite. The encoded protein contained a DNA-binding domain with expected sequence identity (39-58%) to other HSF molecules, and two leucine zipper motifs (LZ123 and LZ4) involved in the oligomerization of HSF. Adult worms express three isoforms of HSF mRNA generated by alternative splicing inside the coding region that contains in-frame splice signals. Introns are not involved in the process since the deleted segments (36 bp or 45 bp) are not flanked by any intron in the gene. Structural variations generated by alternative splicing (insertion of 3 amino acids or 15 amino acids) are continual with LZ4 and added hydrophobic residues are in register with the hydrophobic heptad repeats of LZ4. Structural diversity at the C-terminus of LZ4 may affect the strength of LZ4 interaction with the oligomerization domain (LZ123) and thus modulate the DNA-binding activity of HSF. The conservation of this mechanism in mouse and schistosome may reflect evolutionary pressure to generate multiple HSF species exhibiting functional diversity and capable of responding to different stress signals and physiological signals. Adult worms express HSF mRNA of 2.5 kb, in agreement with the size of the cDNA, while cercariae (developmental stage preceding adult worm) show multiple bands in the range 2.5-3 kb. Available data indicate that the HSF mRNAs of cercariae are inactive. We propose that these mRNA species are generated by an alternative splicing that incorporates introns, which inactivate the mRNA by the insertion of termination codons and/or by shifting of the reading frame. Parasite HSF protein produced in bacteria showed DNA sequence recognition similar to that of HSF in parasite extracts, i.e. the recombinant HSF reacted better with a variant heat-shock element (HSE; one base change in the third NGAAN pentamer of the ideal HSE consensus sequence) than with the ideal HSE. The size of the HSF gene is 12 kb and it is composed of ten exons and nine introns. Excluding the introns, the gene and cDNA show 100% sequence identity. A plant HSF gene contains only a single intron, which matches with the position of intron I2 of schistosome. That the position of this intron is conserved in remote species is indicative of an important function during evolution of the HSF gene.

Alternative Splicing↗
PubMed1995

Isolation of the porcine heparin tetrasaccharides with glucuronate 2-O-sulfate. Heparinase cleaves glucuronate 2-O-sulfate-containing disaccharides in highly sulfated blocks in heparin.

Eleven tetrasaccharides were isolated from the repeating disaccharide region of porcine intestinal heparin after strong digestion with Flavobacterium heparinase. Their structures were determined by composition analysis, enzymatic analysis, and 1H NMR spectroscopy. Nine of them have the common tetrasaccharide backbone, delta HexA alpha 1-4GlcN alpha 1-4IdoA alpha 1-4GlcN, where delta HexA and IdoA represent 4,5-unsaturated hexuronic acid and L-iduronic acid, respectively, and their structural variations are based upon the positions of sulfate groups. The nine compounds include one hexasulfated, three pentasulfated and five tetrasulfated compounds, and four of them have not been isolated previously as discrete structures. The other two of the 11 tetrasaccharides have the following hitherto unreported structures with novel glucuronate 2-O-sulfate at the internal position: delta HexA(2-sulfate) alpha 1- 4GlcN(N,6-disulfate) alpha 1-4GlcA(2-sulfate) beta 1-4GlcN(N-sulfate) and delta HexA(2-sulfate) alpha 1-4GlcN(N,6-disulfate) alpha 1-4GlcA(2-sulfate) beta 1-4GlcN(N,6-disulfate). Thus, 2-O-sulfated glucuronate in the highly sulfated tetrasaccharide structures typical of heparin has been demonstrated. The former and the latter tetrasaccharides account for 0.31 and 0.32% (w/w) of the starting heparin, respectively. Their yield, however, is an underestimation, since these tetrasaccharide structures in longer sequences will be degraded by heparinase. Although the latter tetrasaccharide described above was unexpectedly cleaved by heparinase into two disaccharide units, the former was not degraded by the enzyme most likely due to the lack of the 6-O-sulfate group on the GlcN residue at the reducing terminus. The results indicate its capability of catalyzing both anti and syn elimination, a property shared by heparitinases I and II and chondroitinase ABC. Both tetrasaccharides were degraded into disaccharides by heparitinase II. Therefore, it is necessary to reevaluate the disaccharide composition of heparin/heparan sulfate or oligosaccharide structures, which were previously determined after heparinase or heparitinase II digestion. It is no longer possible to conclude that the 2-O-sulfated unsaturated uronic acid residues obtained from heparin/heparan sulfate by lyase digestions are always derived from iduronate 2-O-sulfate residues in the original polymer. It is quite possible that the novel glucuronate 2-O-sulfate structure in the highly sulfated region of heparin is involved in some of the biological activities of heparin.

Animals↗
PubMed1997

Antigenic variation of the Epstein-Barr virus nuclear antigen EBNA1 as revealed by monoclonal antibodies.

The Epstein Barr virus (EBV) nuclear antigen EBNA1 plays an essential role in the replication of EBV episomes in latently infected cells and is the only viral protein that is consistently expressed in all programs of latent EBV gene expression. In this study, four monoclonal antibodies (MoAbs) directed to a region (amino acid residues 442-530) of EBNA1 were generated. Competitive enzyme-linked immunosorbent assay (ELISA) experiments using biotinylated MoAbs showed that they recognized distinct epitopes. Reactivity of these MoAbs with various laboratory EBV strains and field EBV isolates was shown to be heterogeneous in that EBNA1 from certain strains (isolates) was recognized and that from others was not. All four MoAbs showed such heterogeneous reactivity, and moreover, each MoAb showed a distinct spectrum of reactivity with these EBV strains (isolates). These results demonstrate an extensive structural variation in this region of EBNA1 as predicted by previous sequencing studies. These MoAbs will be useful as probes to dissect this structural heterogeneity of EBNA1.

Animals↗
PubMed2006

Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide.

Recently, chemically synthesized short interfering RNA (siRNA) duplexes have been used with success for gene silencing. Chemical modification is desired for therapeutic applications to improve biostability and pharmacokinetic properties; chemical modification may also provide insight into the mechanism of silencing. siRNA duplexes containing the 2,4-difluorotoluyl ribonucleoside (rF) were synthesized to evaluate the effect of noncanonical nucleoside mimetics on RNA interference. 5'-Modification of the guide strand with rF did not alter silencing relative to unmodified control. Internal uridine to rF substitutions were well-tolerated. Thermal melting analysis showed that the base pair between rF and adenosine (A) was destabilizing relative to a uridine-adenosine pair, although it was slightly less destabilizing than other mismatches. The crystal structure of a duplex containing rFoA pairs showed local structural variations relative to a canonical RNA helix. As the fluorine atoms cannot act as hydrogen bond acceptors and are more hydrophobic than uridine, there was an absence of a well-ordered water structure around the rF residues in both grooves. siRNAs with the rF modification effectively silenced gene expression and offered improved nuclease resistance in serum; therefore, evaluation of this modification in therapeutic siRNAs is warranted.

Base Pairing↗
PubMed1993

Further studies of the structure-activity relationships of 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine. Synthesis and evaluation of 1-(2-benzo[b]thienyl)-N,N-dialkylcyclohexylamines at dopamine uptake and phencyclidine binding sites.

We previously reported (J. Med. Chem. 1993, 36, 1188-1193) that changes to the ring size of the piperidine and cyclohexyl rings of the high-affinity and selective dopamine (DA)-uptake inhibitor 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine (BTCP, 2) caused different, and in some cases opposite, changes in affinity for sites on the DA transporter labeled by [3H]BTCP and [3H]-cocaine. These results suggested that the radioligands label different sites on the transporter. In the present study, we extend the structure-activity relationships (SAR) of BTCP by studying the binding characteristics of a series of N,N-disubstituted 1-(2-benzo[b]thienyl)cyclohexylamines 7-32 at the DA transporter. Cyclohexyl was selected as opposed to other ring sizes since it corresponds to BTCP. The binding results indicate that a considerable degree of structural variation is permitted for the N-substituents, while still retaining nanomolar affinity for sites on the transporter (studied in rat forebrain homogenates). As observed in our earlier study, the differential effects of structural change on binding to sites on the DA transporter labeled by these radioligands suggests that they are different and distinct binding sites. In general, and up to a point, increasing the size and lipophilicity of the N substituents resulted in improvements in binding but appeared to have less predictable effects on DA-uptake inhibition (as measured in rat brain synaptosomes). The binding of these compounds to sites labeled by [3H]BTCP appeared to correlate best with IC50 for DA-uptake inhibition. To our surprise, the monoalkyl N-substituted BTCP derivatives displayed the highest affinity for the DA transporter of all the compounds in this series. For example, the N-(cyclopropylmethyl) derivative 14 displayed IC50's = 23 nM ([3H]cocaine) and 1 nM ([3H]-BTCP), and the N-butyl derivative 10 showed IC50's = 60 nM ([3H]cocaine) and 0.3 nM ([3H]-BTCP). BTCP exhibited IC50's of 39 nM ([3H]cocaine) and 5 nM ([3H]BTCP) in this assay. The observation that N,N-dibutyl derivative 31 exhibited low ratios of IC50 [3H]cocaine/IC50 DA reuptake and IC50 [3H]BTCP/IC50 DA reuptake suggests that it may be a potential candidate for cocaine antagonism studies. The effect of additional amino, amide, and aromatic groups on the N-substituents was examined, and the results are discussed. The failure of all of the compounds in this series to bind phenycyclidine receptors coupled with their high affinity and range of selectivities at the DA transporter identifies many of them as useful tools for probing the mode of action of BTCP at this site.

Animals↗
PubMed2006

Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia.

Infectious agents have been proposed as one of the risk factors for schizophrenia. However, the data on the association of infectious agents with in vivo brain changes are scant. We evaluated the association of serological evidence of exposure to herpes simplex virus 1 (HSV1) with in vivo brain structural variations among first-episode antipsychotic-naive schizophrenia/schizoaffective disorder patients and control subjects. We assayed HSV1 immunoglobulin G (IgG) antibody in serum samples from 30 patients and 44 healthy subjects and obtained structural magnetic resonance imaging scans from the same individuals. There were proportionately more patients with elevated HSV1 antibody ratios than healthy comparison subjects (chi2=3.98, 1 df, P=0.046) and patients had significantly higher HSV1 IgG antibody ratios compared with healthy subjects. Using optimized voxel-based morphometry, we examined diagnosis by HSV1 serological status interaction followed by within- and between-group comparison across the serological status. We observed a diagnosis by HSV1 serological status interaction and a significant main effect of HSV1 serological status in the prefrontal gray matter. Patients exposed to HSV1 had decreased gray matter in Brodmann area 9 (dorsolateral prefrontal cortex) and 32 (anterior cingulate cortex) compared with patients without serological evidence of exposure to HSV1. HSV1-associated differences in brain structure were not detected among healthy subjects. These findings suggest that HSV1 exposure in schizophrenia is associated with specific regional gray matter differences that may not be attributable to medications, illness chronicity or comorbid substance use. This study provides suggestive evidence for a link between HSV1 exposure and some of the cerebral morphological changes often reported in schizophrenia.

Adolescent↗
PubMed1992

An algorithm for comparing RNA secondary structures and searching for similar substructures.

To access the functional informations carried by RNA molecules at the level of their secondary structure interactions, we propose a comparison method based on a tree edit algorithm which takes into account the tree structure of RNA foldings. Any secondary structure is translated into a tree involving all its elementary substructures; then a shorter condensed tree is built in which any unbranched helix interspersed with bulges and interior loops is taken as a single node. This method includes several parameters: a comparison matrix between structural units, gap penalties, and the scoring between nodes of the condensed trees. Their effects have been analysed using as a model a rapidly divergent domain of the large ribosomal RNA, for which structural variation during evolution is well known. This method allows one to recognize precisely, in large target molecules, definite substructures that present with the query molecules only a limited set of closely related secondary structure features; it is still efficient if intervening features, which can correspond to insertion/deletion of entire stem regions, separate such structural elements. When coupled with a hierarchical clustering algorithm, this method is suitable for classifying RNA molecules according to their secondary structure homologies.

Algorithms↗
PubMed2003

Mechanism of the first-order phase transition of an acylurea derivative: observation of intermediate stages of transformation with a detailed temperature-resolved single-crystal diffraction method.

The process of the first-order solid-to-solid phase transition of 1-ethyl-3-(4-methylpentanoyl)urea (1) was observed by means of a detailed temperature-resolved single-crystal diffraction method, which resembles watching a series of stop-motion photographs. The transition consists of two elementary processes, one supramolecular and the other molecular. Crystal structures from before and after the phase transition are isostructural. The straight-ribbon-like one-dimensional hydrogen-bonding structure is formed and stacked to form a molecular layer. The geometry of the layer is retained during the phase transition. The relative position of the layer with its neighbours, on the other hand, changes gradually with increasing temperature. The change is accelerated at the temperature representing the start of the endotherm seen in the DSC curves of (1). The structural variation yields void space between the neighbouring layers. When the void space grows enough that the crystal is unstable, the 3-methylbutyl group on the last of the molecules turns into a disordered structure with drastic conformational changes to fill up the void space. The phase transition process is well supported with simple force-field calculations. A crystal of 1-(4-methylpentanoyl)-3-propylurea (2), which shows no solid-to-solid phase transitions, was also analysed by the same method for comparison.

Journal Article↗
PubMed2000

Hansch analysis of antimalarial cyclic peroxy ketals with physicochemical and electrotopological parameters.

Hansch analysis of some antimalarial cyclic peroxy ketals (IV) having structural variations at the para substituted phenyl ring and an alicyclic ring of different size reveals that electronic and steric parameters of the phenyl ring substituents are important for explaining the variation in the activity while hydrophobicity parameter is of little significance. Electron withdrawing substituents with higher MR (molar refractivity) or V(W) (van der Waals volume) are preferred for the activity. Use of structural descriptors suggests that presence of a seven membered alicyclic ring attached to the peroxy bridge containing ring is conducive to the activity. Application of electrotopological state atom index (ETSAI) suggests a pharmacophore containing the peroxy bridge. This is corroborated by earlier observation on importance of oxygen atoms of the peroxy linkage of artemisinin for antimalarial activity. Although incorporation of ETSAI into Hansch model does not improve the relations, the electronic parameter sigma is found to be significantly correlated with it.

Algorithms↗