Efficiency of hypericum perforatum, povidone iodine, tincture benzoin and tretinoin on wound healing.

Different topical agents have been used to accelerate wound healing. The purpose of this study is to compare the safety and efficacy of topical application of the extract of Hypericum perforatum (HPE), povidone iodine (PI), tincture benzoin (TB) and tretinoin (T) on surgical wound healing. Ten adult female, Wistar albino rats were included in the study. HPE, PI, TB and T solutions were applied on the wounds. After seven days, tissue samples were collected and inflammatory cells, re-epithelialization, granulation tissue, angiogenesis, collagen accumulation, hemorrhage and lysis of cells were investigated histopathologically. No dermal toxicity was noted. HPE, TB, PI have all showed good epithelialization and granulation, but HPE showed the most advanced stage of healing within a short period of time. HPE had significantly higher values of re-epithelialization and collagen accumulation, but lower inflammatory cell count and granulation tissue. TB had the second best in re-epithelialization, collagen accumulation and the highest granulation tissue. PI induced better reepithelialization and granulation than the control group with remarkable cell lysis. As a result, HPE can be a safe, effective, and cheap agent that can be used for surgical wounds.

Synthesis, biological evaluation (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic) and molecular docking study of hydroxy methoxy benzoin/benzil analogous.

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.

Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells.

Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-ß, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.

New antibacterial and 5-lipoxygenase activities of synthetic benzyl phenyl ketones: Biological and docking studies.

We investigated twelve benzyl phenyl ketone derivatives which are synthetic precursors of isoflavonoids that are shown be good 5-hLOX inhibitors, especially those that have the catechol group, but these precursors never have been assayed as 5-hLOX inhibitors being a novelty as inhibitors of the enzyme, due to sharing important structural characteristics. Screening assays, half maximal inhibitory concentration (IC50) and kinetic assays of all the studied molecules (5 µg/ml in media assay) showed that 1-(2,4-dihydroxy-3-methylphenyl)-2-(3-chlorophenyl)-ethanone (K205; IC50 = 3.5 µM; Ki = 4.8 µM) and 1-(2,4-dihydroxy-3-methylphenyl)-2-(2-nitrophenyl)-ethanone (K206; IC50 = 2.3 µM; Ki = 0.7 µM) were potent, selective, competitive and nonredox inhibitors of 5-hLOX. Antioxidant behavior was also assayed by DPPH, FRAP, and assessing ROS production, and those with antibacterial and antiproliferative properties relating to 1-(2,4-dihydroxy-3-methylphenyl)-2-(2-chlorophenyl)-ethanone (K208) established it as the most interesting and relevant compound studied, as it showed nearly 100% inhibition of bacterial growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Finally, docking studies were done that helped to characterize how the inhibitor structures correlated to decreased 5-hLOX activity.

Ligand-Based Drug Design: Synthesis and Biological Evaluation of Substituted Benzoin Derivatives as Potential Antitumor Agents.

BACKGROUND: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. OBJECTIVES: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Kα complex interaction and antiproliferative activity. METHODS: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. RESULTS: A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Kα and estrogen receptor alpha (ERα). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Kα and ERα demonstrated that the series accommodate binding to PI3Kα and/or ERα. CONCLUSION: The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.

Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives targeting innate immune sensors and xanthine oxidase for treatment of gout.

Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6-methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti-hyperuricemic and anti-acute gouty arthritis activities through regulating XOD, NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of anti-gout drugs targeting both innate immune sensors and XOD.

Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3Kα).

The oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has made it an attractive target for anticancer drug design. In this work, we describe our efforts to optimize the lead PI3Kα inhibitor 2-hydroxy-1,2-diphenylethanone (benzoin). A series of 2-oxo-1,2-diphenylethyl benzoate analogs were identified as potential PI3Kα inhibitors. Docking studies confirmed that the aromatic interaction is mediating ligand/protein complex formation and identified Lys802 and Val851 as H-bonding key residues. Our biological data in human colon carcinoma HCT116 showed that the structure analogs inhibited cell proliferation and induced apoptosis.

[Effect of (E)-2-(4-bromophenyl )-1-(3,4-dihydroxyphenyl )ethanone oxime on proliferation and activation of mice lymphocytes].

OBJECTIVE: To study the effects of (E)-2-(4-bromophenyl)-1-(3, 4-dihydroxyphenyl) ethanone oxime (BDEO) on the proliferation and activation of the mice' s splenic lymphocytes and the peripheral blood lymphocytes induced by Concanavalin A (Con A) in vitro and in vivo, and its molecular mechanism. METHODS: During the lymphocyte proliferation and activation induced by Con A in vitro, MTT and cell counting were used to detect the transformation rates and survival rates of lymphocytes, and ELISA was used to measure the activity of caspase-9; moreover, the levels of Bax, Bcl-2 and caspase-3 were determined by Western blot, in order to observe the effects of BDEO on cell proliferation and activation. The effects of administration of Con A [15 mg/(kg x d)] and BDEO [(3, 6 mg/(kg x d)] by intraperitoneal injection on transformation rates of spleen cells and peripheral blood lymphocyte, as well as phagocytosis rate of peritoneal macrophages in mice were also observed in vivo. RESULTS: 0.3-1 micromol/L BDEO significantly inhibited the transformation rates and growth of mice lymphocyte (P < 0.05). The activity of caspase-9 and the levels of mitochondrial pro-apoptotic protein Bax and Bak gradually increased, then decreased as the BDEO continually accumulated. Anti-apoptotic protein Bcl-2 as well as mitochondrial Cyt C levels first decreased then increased gradually, and cytoplasmic Cyt C, cleaved caspase-9 and cleaved caspase-3 levels showed firstly a increase, then decrease gradually. Additionally, administration of BDEO by intraperitoneal injection significantly inhibited proliferation of spleen lymphocytes and peripheral blood lymphocyte, as well as phagocytosis of peritoneal macrophagesin in mice. CONCLUSION: BDEO might regulate the proliferation and activation of lymphocytes through activation of caspase-3 mainly via a mitochondrial intrinsic pathway; the inhibiting effect on the proliferation and transformation rate of lymphocytes was significant when the concentration of BDEO was relatively low; as the concentration accumulated increasingly, the inhibiting effect reduced. The results indicated that BDEO has immunosuppressive activity.

Cytotoxic deoxybenzoins and diphenylethylenes from Arundina graminifolia.

Eight new C-4-alkylated deoxybenzoins (1-8), three new diphenylethylenes (9-11), and five known diphenylethylenes were isolated from Arundina graminifolia. The structures of 1-11 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 9-11 are the first naturally occurring diphenylethylenes possessing a hydroxyethyl unit. Compounds 1-11 were evaluated for cytotoxicity against five human tumor cell lines. Compounds 4, 5, and 9-11 showed significant cytotoxicity against five cancer cell lines, with IC50 values ranging from 1.8 to 8.7 µM.

Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3.

BACKGROUND AND PURPOSE: The melastatin-related transient receptor potential TRPM3 is a calcium-permeable nonselective cation channel that can be activated by the neurosteroid pregnenolone sulphate (PregS) and heat. TRPM3-deficient mice show an impaired perception of noxious heat. Hence, drugs inhibiting TRPM3 possibly get in focus of analgesic therapy. EXPERIMENTAL APPROACH: Fluorometric methods were used to identify novel TRPM3-blocking compounds and to characterize their potency and selectivity to block TRPM3 but not other sensory TRP channels. Biophysical properties of the block were assessed using electrophysiological methods. Single cell calcium measurements confirmed the block of endogenously expressed TRPM3 channels in rat and mouse dorsal root ganglion (DRG) neurones. KEY RESULTS: By screening a compound library, we identified three natural compounds as potent blockers of TRPM3. Naringenin and hesperetin belong to the citrus fruit flavanones, and ononetin is a deoxybenzoin. Eriodictyol, a metabolite of naringenin and hesperetin, was still biologically active as a TRPM3 blocker. The compounds exhibited a marked specificity for recombinant TRPM3 and blocked PregS-induced [Ca(2+)]i signals in freshly isolated DRG neurones. CONCLUSION AND IMPLICATIONS: The data indicate that citrus fruit flavonoids are potent and selective blockers of TRPM3. Their potencies ranged from upper nanomolar to lower micromolar concentrations. Since physiological functions of TRPM3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of TRPM3 in vivo. Considering the involvement of TRPM3 in nociception, TRPM3 blockers may represent a novel concept for analgesic treatment.

Estrogenic effect of three substituted deoxybenzoins.

Deoxybenzoins (1-(2,4-dihydroxyphenyl)-2-(4-hydroxyphenyl)ethanone) are possible precursors or metabolites of isoflavanones which may have xenoestrogenic potential on estrogen receptor (ER). In this study we evaluated three 2'-substituted deoxybenzoin derivatives for their estrogenic effect based upon their ability to affect the proliferation of ERα(+) MCF7 cells, ERß(+) PC3 cells and Hep2 cells stably transfected and expressing either ERα or ERß. These compounds designated as CMPD3, CMPD6 and CMPD9 had -COOH, -(CH(2))(4)-CH(3) and -CH(3) substitutions, respectively on the 2'-position of the 2,4-dihydroxyphenyl ring of deoxybenzoin. We found that all three compounds increased the proliferation of ERα(+) MCF7 cells (EC(50)~1-12 µM) and ERα(+) Hep2 cells, while causing apoptosis in ERß(+) PC3 cells (IC(50)~1-5 µM) and ERß(+) Hep2 cells. The compounds also up-regulated the expression of estrogen sensitive genes, trefoil factor 1 (TFF1, previously known as pS2) and cathepsin-D (CTSD), in these cells. We performed in vitro ER transcription activation assays using Hep2 cells transiently co-transfected with estrogen response element driven luciferase and either ERα or ERß vectors to ascertain the mechanism of action of these compounds through the 'classical' genomic pathway of estrogenic activity and to determine their ER subtype selectivity. Molecular docking of the compounds with the Ligand Binding Domain of ERα and ERß showed similar docking scores (Glidescores of -6.5 to -8.5 kcal/mol) indicating that these compounds were ligands of both ERα and ERß with similar affinity.

The novel phloroglucinol derivative BFP induces apoptosis of glioma cancer through reactive oxygen species and endoplasmic reticulum stress pathways.

Prenyl-phloroglucinol derivatives from hop plants have been shown to have anticancer activities. This study is the first to investigate the anticancer effects of the new phloroglucinol derivative (2,4-bis(4-fluorophenylacetyl)phloroglucinol; BFP). BFP induced cell death and anti-proliferation in three glioma, U251, U87 and C6 cells, but not in primary human astrocytes. BFP-induced concentration-dependently cell death in glioma cells was determined by MTT and SRB assay. Moreover, BFP-induced apoptotic cell death in glioma cells was measured by Hochest 33258 staining and fluorescence-activated cell sorter (FACS) of propidine iodine (PI) analysis. Treatment of U251 human glioma cells with BFP was also found to induce reactive oxygen species (ROS) generation, which was detected by a fluorescence dye used FACS analysis. Treatment of BFP also increased a number of signature endoplasmic reticulum (ER) stress markers glucose-regulated protein (GRP)-78, GRP-94, IRE1, phosphorylation of eukaryotic initiation factor-2α (eIF-2α) and up-regulation of CAAT/enhancer-binding protein homologous protein (CHOP). Moreover, treatment of BFP also increased the down-stream caspase activation, such as pro-caspase-7 and pro-caspase-12 degradation, suggesting the induction of ER stress. Furthermore, BFP also induced caspase-9 and caspase-3 activation as well as up-regulation of cleaved PARP expression. Treatment of antioxidants, or pre-transfection of cells with GRP78 or CHOP siRNA reduced BFP-mediated apoptotic-related protein expression. Taken together, the present study provides evidences to support that ROS generation, GRP78 and CHOP activation are mediating the BFP-induced human glioma cell apoptosis.

Design, synthesis and molecular simulation studies of dihydrostilbene derivatives as potent tyrosinase inhibitors.

The synthesis, molecular modeling and biological evaluation of substituted deoxybenzoins and optimized dihydrostilbenes are reported. Preliminary structure-activity relationship data were elucidated and lead compounds suitable for further optimization were discovered. Dihydrostilbene 7 is a particularly potent inhibitor (IC(50)=8.44 µM, more potent than kojic acid).

Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: structure-activity analysis.

The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.

[Effects of aromatic resuscitation drugs on blood brain barrier in cerebral ischemia-reperfusion injury model rats].

OBJECTIVE: To research the effects of moschus, borneol, styrax and benzoinum on the structure and function of blood brain barrier in cerebral ischemia-reperfusion injury model rats. METHOD: Focal middle cerebral artery occlusion (MCAO) was introduced as an in vivo ischemic model in rats. After 2 h MCAO, nylon suture was pulled up 1 cm to give blood reperfusion. After 22 h reperfusion, all animals were decapitated. The ultramicrostructure of blood brain barrier of ischemia hemisphere side in fronto-parietal cortex region by transmission electron microscope, and the content of VEGF and MMP-9 in ischemia side brain tissue were measured by ELISA. RESULT: In model and solvent group rats, the capillary endothelium cells, astro-glial cells and nerve cells in ischemia hemisphere side in fronto-parietal region were emerged in different degree compared with sham-operated groups, which exhibited tight junction between endothelial cells being opened, basal lamina being dissolved, and permeability increasing, and cellularedema. In borneol (0.2 g x kg(-1)) group rats, the structure of three kinds of cells were nearly normal, which tight junction structure was clear, rough endoplasmic reticulum and polyribosome could be found in cytoplasm. In moschus (66.6 mg x kg(-1)) group rats, the structure of capillary endothelium cells and astrocytes were nearly normal as well as the basal lamina, but the electrons in neurons was maldistribution. In styrax (1.332 g x kg(-1)) group rats, astrocytes were nearly normal, while capillary endothelial cells and neurons exhibited oedema in different degrees. And the basal lamina was discontinuous, augmentation of cell spaces in endothelial cells increased the permeability, some endoplasmic reticulum broadened and ribosome ablated. In benzoinum (1.0 g x kg(-1)) group rats, oedema of capillary endothelial cells and astrocytes was significant, basal lamina broke. Meanwhile endoplasmic reticulum broadened as vacuole, the number of ribosome in rough endoplasmic reticulum decreased, crista mitochondriales in some neurons disappeared as vacuole which hint oedema happened. Results also showed that borneol decrease the level of VEGF in ischemia side brain tissue significantly, while has little influence on the level of MMP-9. Moschus showed the tendency to decrease the level of VEGF and MMP-9 in ischemia side brain tissue. CONCLUSION: Aromatic resuscitation drugs showed the protection effect on blood brain barrier in cerebral ischemia-reperfusion injury rats, which the protection effect of moschus and borneol were better than that of styrax and benzoinum. The mechanism of protection effect maybe related to decrease the level of VEGF and MMP-9.

Synthesis and structure-activity relationship study of deoxybenzoins on relaxing effects of porcine coronary artery.

Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC50=3.30 µM (Emax=100%, n=7) and 2,4-dihydroxy-4'-methoxydeoxybenzoin EC50=3.70 µM (Emax=100%, n=5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure-activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H≥p-OMe>p-OH>o-OMe>m,p-diOMe≥m-OMe.

Design, synthesis and biological evaluation of new (E)- and (Z)-1,2,3-triaryl-2-propen-1-ones as selective COX-2 inhibitors.

A group of (E)-and (Z)-1,2,3-triaryl-2-propen-1-one derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-1 phenyl ring were synthesized and evaluated as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure-activity relationships were determined by varying the substituents on the C-3 propenone moiety. Among the 1,2,3-triaryl-2-propen-1-ones, (Z)-1-(4-(methylsulfonyl)phenyl)-2,3-diphenylprop-2-en-1-one (3b) showed the most potency and selectivity on COX-2 inhibition (COX-2 IC(50) = 0.07 microM; selectivity index = 201). The Z-propenones were also found to be more potent and selective than their E-isomers for COX-2 inhibitory activity. The structure-activity data acquired indicate that the geometry of propenone and also the type of substituents on the C-3 propenone are important for COX-2 inhibitory activity.

Isolation of 2,4,4'-trihydroxydeoxybenzoin and 3'-hydroxydaidzein from soybean miso.

Two 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging compounds were isolated from soybean miso. They were determined to be 2,4,4'-trihydroxydeoxybenzoin and 3'-hydroxydaidzein on the basis of spectroscopic data. In the manufacturing process for soybean miso, 2,4,4'-trihydroxydeoxybenzoin appeared during culture aging, and the quantity of it increased in a time-dependent manner.

Metronidazole-deoxybenzoin derivatives as anti-Helicobacter pylori agents with potent inhibitory activity against HPE-induced interleukin-8.

A series of new metronidazole-deoxybenzoin derivatives were synthesized and evaluated for their antimicrobial activity against Helicobacter pylori. Highly selective anti-H. pylori activity was also observed in synthesized compounds. Compound 34 exhibited the most potent activity, similar to the positive control amoxicillin. Furthermore, compounds 17 and 34 were able to significantly decrease H. pylori water extract (HPE)-induced production of interleukin-8 (IL-8) in gastric mucosal cells, which did not show any effect on the cell viability.

Design and synthesis of novel deoxybenzoin derivatives as FabH inhibitors and anti-inflammatory agents.

Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. The synthesis and biological evaluation halide-deoxybenzoins derivatives are described in this Letter. Potent FabH inhibitory and selective anti-Gram-negative bacteria activities were observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on the biological data and molecular docking, compound 19 is a potential FabH inhibitor and anti-inflammatory agent deserving further research.