Relationship Of Chemical Structure Research Articles

Synthesis and in vitro Activity of Eugenyl Benzoate Derivatives as BCL-2 Inhibitor in Colorectal Cancer with QSAR and Molecular Docking Approach.

This study is aimed to acquiring new compounds of Eugenyl benzoate (2-methoxy-4-(prop-2-en-1-yl)phenyl benzoate) derivatives that can inhibit HT29 colorectal cancer cells. In this research, we used several chemical reactions to synthesize novel compounds, such as Esterification, Demethylation, Halohydrin, and Sharpless reaction. Cytotoxicity assays were performed to test the inhibitory activity of compounds against HT29 colon cancer cells. QSAR analysis were carried out to analyse the relationship of chemical structure of the novel compounds with their cytotoxic activity. Ten novel compounds were successfully synthesized and tested in vitro against the HT29 cell. The IC50 of the novel compounds were between 26.56 µmol/ml - 286.81 µmol/ml which compound 4-[(2S)-2,3-dihydroxypropyl]-2-methoxyphenyl 2-hydroxybenzoate (9) showed as best active compound as BCL-2 inhibitors better than other synthesized compounds and Eugenol as well. QSAR analysis of the in vitro results gave a Log equation: 1/IC50 = -0.865-0.210 (LogP)2 + 1,264 (logP)-0.994 CMR (n = 10; r = 0.706; SE: 0.21; F = 0.497, sig = 7.86). The equation shows the log variable P and CMR affect IC50. The properties of hydrophobicity (log P) are more instrumental than the ones of steric (CMR). The active compound (9) given best activities as BCL-2 inhibitors than other eugenol derivatives. QSAR indicates the logP and CMR have effect on its colorectal cytotoxic activity which the hydrophobicity parameter (logP) plays more role than the steric parameter (CMR).

Renewable atom-efficient dendrimer-like acetate: from toxic tung oil to non-toxic plasticizers

Over the last 60 years, phthalate plasticizer production has increased manifold, owing to their inexpensive, multipurpose, durable, and lightweight nature. These characteristics have raised the demand for phthalate plasticizers that will continue to grow over the coming years. However, with increased phthalate plasticizer production comes increased water pollution and soil pollution, as well as serious harm to human health. The recent studies mainly focused on plasticizing properties, plasticizing mechanism, and raw material sources, but the relationship of chemical structure of the plasticizer and its toxicity has never been reported. In this study, we synthesized three kinds of renewable atom-efficient dendrimer-like plasticizers based on toxic tung oil (DPTs). Plasticizing properties, plasticizing mechanism, and toxicity of DPTs were investigated. The results showed that polyvinyl chloride (PVC)/40 phr DPT has superior plasticizing properties and migration resistance than PVC/40 phr dioctyl phthalate. All DPT plasticizers have toxic doses of 5000 mg/kg and are non-toxic. These DPTs are potential to replace reproductive toxic phthalate plasticizers in food packaging materials, toys, and medical equipment.

Benzothiadiazole-based non-fullerene acceptors

The power conversion efficiencies (PCEs) of organic solar cells (OSCs) have been greatly improved with the rapid development of non-fullerene acceptors (NFAs) in recent five years. Among a great deal of electron-accepting units (A units), benzothiadiazole (BT) is the most important one and has been widely used to construct high-efficiency NFAs due to its unique electron-withdrawing properties, plane rigidity and structural adjustability. The optoelectronic properties of BT-based small molecules can be efficiently modulated with the location of BT unit in the molecular backbone. Typically, BT unit is used as an A 1 unit to construct A 2 -D-A 1 -D-A 2 and A 2 -A 1 -D-A 1 -A 2 type acceptors. Furthermore, DA’ D -type fused BT-units can be utilized as a central segment to design A-DA’D-A type NFAs, which promote the rapid progress of OSCs from 2019. Judicious molecular engineering can finetune the energy levels of frontier molecular orbitals, absorption spectra, and the π-π staking properties of these materials. In turn, high-efficiency photovoltaic devices can be obtained by combining these BT-based NFAs with suitable p-type polymers. The highest PCE of OSC reached up to 18%, which could be mainly attributed to the emerge of the fused-BT-based molecule Y6. This review firstly made a precise classification of BT-based NFAs, and then summarized the relationship of chemical structures, molecular properties, and device performance. Finally, we looked forward to the challenges and design directions of this kind of molecules in the future. Benzothiadiazole (BT) is the most important electron-accepting (A) unit and has been widely used to construct high-efficiency non-fullerene acceptors (NFAs). This review firstly made a precise classification of BT-based NFAs: single-BT, double-BT, multiple-BT and ring-fused BT. Then, we summarized the relationship of chemical structures, molecular properties, energy loss and photovoltaic performance. Finally, the challenges and design directions of this kind of molecules are prospected. • A comprehensive review on the development of BT-based non-fullerene acceptors (NFAs) was made. • BT-based acceptor is an eximious material to obtain power conversion efficiency of more than 18%. • This kind of acceptor has been systematically classified and the structure-property relationships were deeply summarized. • An innovative prospect for the future development and the direction of industrialization of BT-based acceptors was made.

Recent progress on all‐small molecule organic solar cells using small‐molecule nonfullerene acceptors

AbstractRecently, solution‐processed organic solar cells combining small‐molecule donor and nonfullerene acceptor have achieved breakthrough results with the certified efficiency over 15%. These impressive progresses are driven by the concerted efforts of modifying the donor and acceptor materials and optimizing the morphology. Considering the defined chemical structures and easily tuned properties of small‐molecule materials, it is of great necessity and importance to pay more attentions on the topic of all‐small molecule organic solar cells. Here, we summarize the recent progress of all‐small molecule organic solar cells from the prospect of materials' evolutions and expect to provide some hints for its future developments. The involved small‐molecule donors including oligothiophene‐, benzodithiophene‐, naphthodithiophene‐, and porphyrin‐based materials are discussed to illustrate the relationship of chemical structures, properties, and device performance. Then, the small‐molecule nonfullerene acceptors in all‐small molecules organic solar cells are discussed to highlight their vital role. Finally, we will present the challenges and future of this research area.image

Secondary Metabolite Produced by Diaporthe terebinthifolli LGMF658 – Bioactivity and Chemical Structure Relationship

Background: Motivated by the need for bioprospecting new drug studies have revealed a variety of secondary metabolites with biological activity. In particular, antimicrobial research confronts the growing reality of resistance of microorganisms to currently available drugs. Modifications in the chemical structure of secondary metabolites may be important in the development of a product to improve the efficacy of these compounds. Being cognizant of the fact that modifications in the chemical structure could enhance the biological activity and improve the compound characteristics for the development of a product, the present study aimed to verify, if there is the possibility of a significant difference in the bioactivity of verbanol in relation to verbenol. Methods: The biological activity was evaluated by agar diffusion assay and microdilution. Results: Verbanol is a bioactive secondary metabolite produced by the endophytic fungus Diaporthe terebinthifolli LGMF658. This compound has bactericidal activity against Staphylococcus aureus and fungicide against Candida albicans according to the microdilution assay. Discussion: In contrast, verbenol, a byproduct of verbanol, did not control the development of the bacterium and showed fungistatic activity against yeast. Conclusion: The results demonstrated that the presence of the double bond, which increased the polarity of the compound, reduced its bioactivity, corroborating with other studies that report the importance of lipophilicity for antimicrobial action.

Organic chemical structure relationships to maturity and stability in shales

The systematic understanding of organic matter chemical structure-thermal stability relationships is central to resource outcomes in sedimentary basins. This study integrates molecular spectroscopy (solid-state 13C NMR) and step-wise isothermal analysis (isoTGA) in elucidating key structure-maturity-stability relationships in shales containing type I and II kerogens (Green River and Eagle Ford Formations, respectively) that were subjected to simulated maturation via hydrous pyrolysis. Hydrous pyrolysis temperatures ranged from 250 to 400 °C – the window for immature to oil generation in the catagenic process (corresponding to Easy %Ro 0.36 to 1.07). Specifically, mole fraction aromatic C (fa) revealed strong correlations with pyrolysis temperature across both kerogen types, increasing 14.8 to 44.9 mol% and 19.7 to 75.2 mol% in the Green River and Eagle Ford samples, respectively. Aromatic bridgehead C (faB), a measure of aromatic ring condensation, showed limited predictive variation with maturity. The increase in aromatization/condensation was accompanied by increased pyrolytic cracking of alkyl C (fal), which decreased from 66.2 to 42.9 mol% in the Green River and 56.1 to 12.2 mol% in the Eagle Ford kerogen. Our 13C NMR analyses of the kerogens revealed empirical relationships that can be used for predicting pyrolysis temperature and maturity (Easy %Ro) based on the major organic structural properties of kerogen. Step-wise, isothermal thermogravimetric analyses allowed for the estimation of kinetic parameters associated with catagenesis: activation energy (Ea) and frequency factor (A). Thermal decomposition of kerogen was revealed to be a two-stage process, and increasing maturity generally resulted in an increase of thermal stability/activation energy. First-stage activation energies (Ea1) ranged 64.0 to 44.7 kJ mol−1, while second-stage activation energies (Ea2) ranged 151.4 to 198.9 kJ mol−1 with increasing maturity in the Green River samples. Similarly, Ea1 and Ea2 of the Eagle Ford ranged 13.1 to 46.0 kJ mol−1 and 208.0 to 286.2 kJ mol−1, respectively. The quantitative determination of covariation in organic structure and thermal stability of kerogen with increasing maturity can be useful in further parameterizing Basin and Petroleum System Models (BPSMs). Furthermore, these results can support the development of computational models of petroleum generation and further facilitate the experimentally-driven understanding of the interplay between organic structure and thermal stability in petroleum systems.

The novel platinum(IV) prodrug with self-assembly property and structure-transformable character against triple-negative breast cancer

Herein, a small library of Pt(IV) prodrugs based on cisplatin and chemosensitizer adjudin (ADD) were explored for efficient cisplatin resistant triple-negative breast cancer (TNBC) treatment. We further elucidated the detail relationship of chemical structure, alkyl chain length (ethyl to dodecyl) and ADD substituted degree, with respect to the self-assembly ability and cytotoxic effect of prodrugs. It demonstrated that all prodrugs could self-assemble into nanomedicine, which was in consist with the molecule structure building and self-assembly simulation. All nanomedicines possessed small particle size, uniform morphology and ultra-high drug loading content (84.0%–86.5%). Moreover, the length of alkyl chain was of great importance for the structure-transformable character and cytotoxicity of nanomedicines. Interestingly, ADD monosubstituted with butyl or hexyl contralateral substituted prodrug (C4-Pt-ADD or C6-Pt-ADD) assembled nanomedicine could convert to wire or sheet structure. These transformable nanoparticles showed great potential in improving the sensitivity of cisplatin to TNBC with up to 266-fold lower IC50 value and significantly enhanced in vivo tumor growth inhibition. Therefore, the self-assembled nanomedicine based on Pt(IV)-ADD could be a promising strategy for TNBC therapy.

Discovery of potent PTP1B inhibitors via structure-based drug design, synthesis and in vitro bioassay of Norathyriol derivatives

Protein tyrosine phosphatase 1B (PTP1B) has recently been identified as a potential target of Norathyriol. Unfortunately, Norathyriol is not a potent PTP1B inhibitor, which somewhat hinders its further application. Based on the fact that no study on the relationship of chemical structure and PTP1B inhibitory activity of Norathyriol has been reported so far, we attempted to perform structural optimization so as to improve the potency for PTP1B. Via structure-based drug design (SBDD), a rational strategy based on the binding mode of Norathyriol to PTP1B, we designed 26 derivatives with substitutions at the four phenolic hydroxyl groups of Norathyriol. By chemical synthesis and in vitro bioassay, we identified seven PTP1B inhibitors that were more potent than Norathyriol, of which XWJ24 showed the highest potency (IC50: 0.6 μM). We also found out that XWJ24 was a competitive inhibitor and showed the 4.5-fold selectivity over its close homolog, TC-PTP. Through molecular docking of XWJ24 against PTP1B, we highlighted the essential role of its hydrogen bond with Asp181 for PTP1B inhibition and identified a potential halogen bond with Asp48 that was not observed for Norathyriol. The current data indicate that our SBDD strategy is effective to discover potent PTP1B-targeted Norathyriol derivatives, and XWJ24 is a promising lead compound for further development.

Cardo Copolymers: A Friction–Chemical Structure Relationship

Poly(arylene ether ketone)s containing pendent bulky cardo groups in the monomer unit, while having a high antifrictionality, do not obey the earlier established regularity of the relationship between chemical structure and friction. The necessity of taking into account the flexibility of macromolecules is an additional factor for these polymers. To XPS study the tribochemical processes of carded polymers, “flexible chain” and “rigid chain” copolyarylene ether ketones (co-PAEKs) were used. It was found that the flexible moieties of the macromolecule favor a decrease in the friction coefficient and an increase in the wear resistance. Impaired tribochemical indices of the rigid cardo polymer are caused by active tribodestruction of phthalimidine groups.

De Novo Design, Synthesis, and Biological Evaluation of 3,4-Disubstituted Pyrrolidine Sulfonamides as Potent and Selective Glycine Transporter 1 Competitive Inhibitors.

The development of glycine transporter 1 (GlyT1) inhibitors may offer putative treatments for schizophrenia and other disorders associated with hypofunction of the glutaminergic N-methyl-d-aspartate (NMDA) receptor. Herein, we describe the synthesis and biological evaluation of a series of 3,4-disubstituted pyrrolidine sulfonamides as competitive GlyT1 inhibitors that arose from de novo scaffold design. Relationship of chemical structure to drug-drug interaction (DDI) and bioactivation was mechanistically investigated. Murine studies were strategically incorporated into the screening funnel to provide early assessments of in vivo target occupancy (TO) by ex vivo binding studies. Advanced compounds derived from iterative structure-activity relationship (SAR) studies possessed high potency in ex vivo binding studies and good brain penetration, promising preliminary in vivo efficacy, acceptable preclinical pharmacokinetics, and manageable DDI and bioactivation liabilities.

Benzocyclobutene organosiloxane resins prepared by alcoholysis of BCB functionalized chlorosilane for highly crosslinked low-k thermosets

In this paper, highly crosslinked benzocyclobutene (BCB) organosiloxane intrinsic low-k thermosets with high thermal stability were prepared by thermal-curing of BCB organosiloxane resins, which were synthesized by alcoholysis of BCB functionalized chlorosilane (BCS) with silanol. Firstly, BCS was prepared by dichloromethylvinylsilane with 4Br-BCB by Grignard reaction. 1,4-Phenylenebis(dimethylsilanol), [1,1′-biphenyl]-4,4′-diylbis(dimethylsilanol) and diphenylsilanediol as silanol precursors were reacted with BCS to prepare BCB organosiloxane resins. These resins could be cured above 200°C to prepare highly cross-linked thermosets with high thermal stability with Td5 above 450°C. DMA studies showed that these thermosets show high Tg above 250°C. The cured resins showed relative low dielectric constant and dissipation loss. Typically, the resin with silbiphenylene structure showed a dielectric constant of 2.69. Meanwhile, the relationship of chemical structure and properties of the cured resins were discussed, especially in the dynamic mechanical analysis and dielectric properties. These cured resins with good dielectric properties and high thermal stability can be a promising candidate for interlayer dielectric materials in semiconductor packaging.

The Influence of Fluorination on Nano-Scale Phase Separation and Photovoltaic Performance of Small Molecular/PC71BM Blends.

To investigate the fluorination influence on the photovoltaic performance of small molecular based organic solar cells (OSCs), six small molecules based on 2,1,3-benzothiadiazole (BT), and diketopyrrolopyrrole (DPP) as core and fluorinated phenyl (DFP) and triphenyl amine (TPA) as different terminal units (DFP-BT-DFP, DFP-BT-TPA, TPA-BT-TPA, DFP-DPP-DFP, DFP-DPP-TPA, and TPA-DPP-TPA) were synthesized. With one or two fluorinated phenyl as the end group(s), HOMO level of BT and DPP based small molecular donors were gradually decreased, inducing high open circuit voltage for fluorinated phenyl based OSCs. DFP-BT-TPA and DFP-DPP-TPA based blend films both displayed stronger nano-scale aggregation in comparison to TPA-BT-TPA and TPA-DPP-TPA, respectively, which would also lead to higher hole motilities in devices. Ultimately, improved power conversion efficiency (PCE) of 2.17% and 1.22% was acquired for DFP-BT-TPA and DFP-DPP-TPA based devices, respectively. These results demonstrated that the nano-scale aggregation size of small molecules in photovoltaic devices could be significantly enhanced by introducing a fluorine atom at the donor unit of small molecules, which will provide understanding about the relationship of chemical structure and nano-scale phase separation in OSCs.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues

BackgroundDihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. MethodsDHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance (1H and 13C), andmass spectrometry analysiswere used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4h after pleurisy induction. ResultsDHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration andMPOactivity (p<0.05). OnlyDHCsignificantly decreased the exudate concentrations (p<0.01). ConclusionsDHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan.We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Implementation of a High-Throughput Screen for Identifying Small Molecules to Activate the Keap1-Nrf2-ARE Pathway

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes involved in antioxidant defense through binding to Antioxidant Response Elements (ARE) located in the promoter regions of these genes. To identify Nrf2 activators for the treatment of oxidative/electrophilic stress-induced diseases, the present study developed a high-throughput assay to evaluate Nrf2 activation using AREc32 cells that contain a luciferase gene under the control of ARE promoters. Of the 47,000 compounds screened, 238 (top 0.5% hits) of the chemicals increased the luminescent signal more than 14.4-fold and were re-tested at eleven concentrations in a range of 0.01–30 µM. Of these 238 compounds, 231 (96%) increased the luminescence signal in a concentration-dependent manner. Chemical structure relationship analysis of these 231 compounds indicated enrichment of four chemical scaffolds (diaryl amides and diaryl ureas, oxazoles and thiazoles, pyranones and thiapyranones, and pyridinones and pyridazinones). In addition, 30 of these 231 compounds were highly effective and/or potent in activating Nrf2, with a greater than 80-fold increase in luminescence, or an EC50 lower than 1.6 µM. These top 30 compounds were also screened in Hepa1c1c7 cells for an increase in Nqo1 mRNA, the prototypical Nrf2-target gene. Of these 30 compounds, 17 increased Nqo1 mRNA in a concentration-dependent manner. In conclusion, the present study documents the development, implementation, and validation of a high-throughput screen to identify activators of the Keap1-Nrf2-ARE pathway. Results from this screening identified Nrf2 activators, and provide novel insights into chemical scaffolds that might prevent oxidative/electrophilic stress-induced toxicity and carcinogenesis.

SARConnect: A Tool to Interrogate the Connectivity Between Proteins, Chemical Structures and Activity Data.

The access and use of large-scale structure-activity relationships (SAR) is increasing as the range of targets and availability of bioactive compound-to-protein mappings expands. However, effective exploitation requires merging and normalisation of activity data, mappings to target classifications as well as visual display of chemical structure relationships. This work describes the development of the application “SARConnect” to address these issues. We discuss options for delivery and analysis of large-scale SAR data together with a set of use-cases to illustrate the design choices and utility. The main activity sources of ChEMBL,1 GOSTAR2 and AstraZeneca’s internal system IBIS, had already been integrated in Chemistry Connect.3 For target relationships we selected human UniProtKB/Swiss-Prot4 as our primary source of a heuristic target classification. Similarly, to explore chemical relationships we combined several methods for framework and scaffold analysis into a unified, hierarchical classification where ease of navigation was the primary goal. An application was built on TIBCO Spotfire to retrieve data for visual display. Consequently, users can explore relationships between target, activity and structure across internal, external and commercial sources that encompass approximately 3 million compounds, 2000 human proteins and 10 million activity values. Examples showing the utility of the application are given.

ChemInform Abstract: Two Rings in Them All: The Labdane‐Related Diterpenoids

AbstractReview: 75 refs.

Two rings in them all: The labdane-related diterpenoids

In his original exposition of the biogenetic isoprenoid rule, L. Ruzicka noted the structural identity between the fused A/B rings of triterpenoids/sterols and certain multicyclic diterpenoids as part of the impetus leading to that profound insight. His prescient hypothesis that this chemical structure relationship reflects similarities in the initial cyclization of these diterpenoids with that occurring in triterpenoid biosynthesis has since been verified. However, this chemical structure relationship does not continue to hold true for the additional rings found in many of these di- and tri- terpenoid natural products. This is now appreciated to arise from differences in their subsequent biogenesis, specifically further cyclization and/or rearrangement of these diterpenoids after formation of an initial bicyclic intermediate in a separately catalyzed reaction. The trivial name for the hydrocarbon skeleton of the most commonly found version of the corresponding unique intermediate forms the basis for a unifying “labdane-related” designation. This defines a large super-family of diterpenoids that contains nearly 7,000 already known natural products. Many of these are found in plants, where the requisite biosynthetic machinery for gibberellin phytohormones, particularly the relevant diterpene cyclases, provides a biosynthetic reservoir that appears to have been repeatedly drawn upon to evolve new labdane-related diterpenoids. The potent biological activity of the “ancestral” gibberellins, which has led to the independent evolution of distinct gibberellin biosynthetic pathways in plants, fungi, and bacteria, is further discussed as an archetypical example of the selective pressure driving the observed diversification of the large super-family of labdane-related diterpenoid natural products.

Substituent Effects of Pterin Derivatives on Singlet Oxygen Scavenging Activity

The relationship of chemical structures of 6-formylpterin (6FP) and its derivatives with scavenging activity of singlet oxygen ((1)O(2)) was examined. First, effects of pterin derivatives on (1)O(2) released from activated human neutrophils were examined. The neutrophils, stimulated with opsonized zymosan, released (1)O(2) that was detected by chemiluminescence using a (1)O(2) specific probe, trans-1-(2'-methoxyvinyl)pyrene. 6FP and its derivatives suppressed the (1)O(2) release. 6FP and other commercially available pterin derivatives, such as biopterin and neopterin, which have different substitutions at the 6-position, suppressed the (1)O(2) release with similar extent. On the other hand, newly synthesized pterin derivatives, which have different substitutions at the 2- and/or 3-position, such as 2-amino-6-formyl-3-methylpteridin-4-one, suppressed the (1)O(2) release in a dose-dependent manner and more potently than 6FP. Then, the (1)O(2) scavenging activity of pterin derivatives was examined photochemically by direct analysis of near-infrared luminescence at 1270 nm, the most sensitive method for the detection of (1)O(2). When rose Bengal, a photosensitizer, in D(2)O solution, was irradiated by 514 nm laser beam, the emission spectrum of (1)O(2) was observed. 6FP suppressed this emission spectrum of (1)O(2), and the newly synthesized pterin derivatives with different substituent at the 2- and/or 3-position suppressed the spectrum more potently than 6FP. The order of potency was similar to that obtained from biological assays. These findings indicate that the substitutions at the 2- and/or 3-position play an important role in (1)O(2) scavenging activity of pterin derivatives.

Isolation, structure and biological activities of platensimycin B4 from Streptomyces platensis

Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of platensimycin by chemical screening led to the isolation of platensimycin B(4), a glucoside congener of platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.

Antiosteoporotic activity of phenolic compounds from Curculigo orchioides

Six phenolic compounds isolated from Curculigo orchioides, including 2,6-dimethoxy benzoic acid (1), curculigoside A (2), curculigoside B (3), curculigine A (4), curculigine D (5) and 3,3',5,5'-tetramethoxy-7,9':7',9-diepoxylignan-4,4'-di-O-beta-D-glucopyranoside (6), together with the ethanol extract of Curculigo orchioides were evaluated for their activity on osteoblasts in neonatal rat calvaria cultures and multinucleated osteoclasts derived from rat marrow cells so as to characterize the antiosteoporotic components of this plant and explore the relationship of chemical structure with antiosteoporotic activity. The proliferation of osteoblast was assayed by MTT methods. The activity of ALP (alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) was measured by p-nitrophenyl sodium phosphate assay. The TRAP stain was used to identify osteoclast in morphology. The resorption pit area on the bone slices formed by osteoclast was measured by computer image processing. The ethanol extract exhibited stimulatory effect on both the osteoblast proliferation and the ALP activity. Six compounds all increased the osteoblast proliferation, and compounds (1), (2) and (4) also slightly increased the osteoblastic ALP activity. Compounds (1), (2), (3), (6) and the ethanol extract decreased area of bone resorption pit, osteoclastic formation and TRAP activity. These results indicated that phenolic compounds are antiosteoporotic chemical constituents from Curculigo orchioides, and their activities are related with chemical structures.