Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase.

Plasmodium falciparum's resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.

The effects of TPL-PEI-CyD on suppressing performance of MCF-7 stem cells.

Triptolide, an ingredient of Tripterygium wilfordii, has been demonstrated to possess many biological activities such as immunomodulatory, antitumor activity in experiment. The purpose of this study was to survey the toxicity of TPL-PEI-CyD on renal cells and its effects on breast carcinoma stem cells. The cytotoxicity of TPL-PEI-CyD and TPL on HK-2 was comparatively assessed by CCK-8. After incubation and culturing with TGF-ß1, the MCF-7 cells were assessed by flow cytometry for the proportion of CD44+> CD24- cells; then the CD44>+> CD24- cells were sorted by immunomagnetic beads as MCF-7 stem cells. To assess the effect of TPL-PEI-CyD on MCF-7 stem cells, Western Blot was used to detect the expression of Oct-4 and ALDHl in MCF-7 stem cells after being dosed with TPL- PEI-CyD. Results showed that, compared with TPL, the toxicity of TPL-PEI-CyD on HK-2 cells was significantly reduced (P<0.05). Breast carcinoma stem cells can be enriched by TGF-ß1 and isolated from MCF-7 cells by immunomagnetic sorting. TPL- PEI-CyD can even more significantly suppress the expression of Oct-4 and ALDHA1 in MCF-7 stem cells than TPL (P<0.05). In conclusion, after coupling TPL and PEI-CyD, TPL-PEI-CyD showed characteristics of effective suppression to breast carcinoma stem cell and decrease of cytotoxicity. It presented the unique effect of traditional Chinese medicine as an efficient and low toxic drug carrier complex for breast carcinoma treatment.

Heterobinuclear copper(II)­platinum(II) complexes with oxindolimine ligands: Interactions with DNA, and inhibition of kinase and alkaline phosphatase proteins.

Two mononuclear copper(II) compounds, [Cu(isad)(H2O)Cl]Cl 1 and [Cu(isah)(H2O)Cl]Cl 2, and its corresponding heterobinuclear species containing also platinum(II), [CuCl(isad)Pt(NH3)Cl2] 3 and [CuCl(isah)Pt(NH3)Cl2] 4 (where isad and isah are oxindolimine ligands, (E)-3-(2-(3-aminopropylamino)ethylimino)indolin-2-one, and (E)-3-(3-amino-2-hydroxypropylimino)indolin-2-one, respectively), have been previously synthesized and characterized by different spectroscopic techniques in our laboratory. Cytotoxicity assays performed with B16F10 murine cancer cells, and MES-SA human uterine sarcoma cells, showed IC50 values lower or in the same order of cisplatin. Herein, in order to better elucidate their probable modes of action, possible interaction and damage to DNA, as well as their effect on the activity of crucial proteins were verified. Both mononuclear complexes and the binuclear compound 4 displayed a significant cleavage activity toward plasmid DNA, while compound 3 tends to protect DNA from oxidative damage, avoiding degradation. Complementary experiments indicated a significant inhibition activity toward cyclin-dependent kinase (CDK1/cyclinB) activity in the phosphorylation of histone H1, and only moderate inhibition concerning alkaline phosphatase. Results also revealed that the reactivity is reliant on the ligand structure and on the nature of the metal present, in a synergistic effect. Simulation studies complemented and supported our results, indicating different bindings of the binuclear compounds to DNA. Therefore, the verified cytotoxicity of these complexes comprises multiple modes of action, including modification of DNA conformation, scission of DNA strands by reactive oxygen species, and inhibition of selected proteins that are crucial to the cellular cycle.

The Spirocyclic Imine from a Marine Benthic Dinoflagellate, Portimine, Is a Potent Anti-Human Immunodeficiency Virus Type 1 Therapeutic Lead Compound.

In this study, we aimed to find chemicals from lower sea animals with defensive effects against human immunodeficiency virus type 1 (HIV-1). A library of marine natural products consisting of 80 compounds was screened for activity against HIV-1 infection using a luciferase-encoding HIV-1 vector. We identified five compounds that decreased luciferase activity in the vector-inoculated cells. In particular, portimine, isolated from the benthic dinoflagellate Vulcanodinium rugosum, exhibited significant anti-HIV-1 activity. Portimine inhibited viral infection with an 50% inhibitory concentration (IC50) value of 4.1 nM and had no cytotoxic effect on the host cells at concentrations less than 200 nM. Portimine also inhibited vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped HIV-1 vector infection. This result suggested that portimine mainly targeted HIV-1 Gag or Pol protein. To analyse which replication steps portimine affects, luciferase sequences were amplified by semi-quantitative PCR in total DNA. This analysis revealed that portimine inhibits HIV-1 vector infection before or at the reverse transcription step. Portimine has also been shown to have a direct effect on reverse transcriptase using an in vitro reverse transcriptase assay. Portimine efficiently inhibited HIV-1 replication and is a potent lead compound for developing novel therapeutic drugs against HIV-1-induced diseases.

Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.

BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.

Synthesis and Biological Evaluation of Imines Structurally Related to Resveratrol as Dual Inhibitors of VEGF Protein Secretion and hTERT Gene Expression.

A group of 28 N-benzylidene aniline derivatives structurally related to the natural stilbene resveratrol has been prepared through condensation of anilines with the corresponding aldehydes. The ability of these imines to inhibit proliferation of two tumor cell lines (HT-29 and MCF-7) and one non-tumor cell line (HEK- 293) was first determined. Subsequently, we determined the ability of some of the most cytotoxic compounds to inhibit the secretion of the VEGF-A factor in HT-29 cells and to downregulate the expression of the VEGF and hTERT genes, the latter one being involved in the activation of telomerase.

EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

UNLABELLED: L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. AIM: Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. MATERIAL AND METHODS: The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. RESULTS: It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). CONCLUSIONS: Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1D Adrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities.

A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- and α1B-AR through screening of an in-house compound library. From initial structure-activity relationship studies, we found lead compound 9m with hERG K(+) channel liability. To develop analogues with reduced hERG K(+) channel inhibition, a combination of site-directed mutagenesis and docking studies was employed. Further optimization led to the discovery of (R)-9s and 9u, which showed antagonistic activity by a bladder strip test in rats with bladder outlet obstruction, as well as ameliorated cystitis-induced urinary frequency in rats. Ultimately, 9u was selected as a clinical candidate. This is the first study to show the utility of iminopyridine derivatives as selective α1D-AR antagonists and evaluate their effects in vivo.

A new role for AMP-activated protein kinase in the circadian regulation of L-type voltage-gated calcium channels in late-stage embryonic retinal photoreceptors.

AMP-activated protein kinase (AMPK) is a cellular energy sensor, which is activated when the intracellular ATP production decreases. The activities of AMPK display circadian rhythms in various organs and tissues, indicating that AMPK is involved in the circadian regulation of cellular metabolism. In vertebrate retina, the circadian clocks regulate many aspects of retinal function and physiology, including light/dark adaption, but whether and how AMPK was involved in the retinal circadian rhythm was not known. We hypothesized that the activation of AMPK (measured as phosphorylated AMPK) in the retina was under circadian control, and AMPK might interact with other intracellular signaling molecules to regulate photoreceptor physiology. We combined ATP assays, western blots, immunostaining, patch-clamp recordings, and pharmacological treatments to decipher the role of AMPK in the circadian regulation of photoreceptor physiology. We found that the overall retinal ATP content displayed a diurnal rhythm that peaked at early night, which was nearly anti-phase to the diurnal and circadian rhythms of AMPK phosphorylation. AMPK was also involved in the circadian phase-dependent regulation of photoreceptor L-type voltage-gated calcium channels (L-VGCCs), the ion channel essential for sustained neurotransmitter release. The activation of AMPK dampened the L-VGCC currents at night with a corresponding decrease in protein expression of the L-VGCCα1 pore-forming subunit, while inhibition of AMPK increased the L-VGCC current during the day. AMPK appeared to be upstream of extracellular-signal-regulated kinase and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Hence, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology. We found that in chicken embryonic retina, the activation of AMP-activated protein kinase (AMPK) is under circadian control and anti-phase to the retinal ATP rhythm. While ATP content is higher at night, phosphorylated AMPK (pAMPK) is higher during the day. AMPK appears to be upstream of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and mammalian target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Therefore, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology.

The protective effects of oxyresveratrol imine derivative against hydrogen peroxide-induced cell death in PC12 cells.

Oxyresveratrol (2',3,4',5-tetrahydroxystilbene) is a naturally occurring ingredient found in mulberries that shows potential as an antioxidant, anti-inflammatory, and neuroprotective agent. This study was performed to identify materials similar to oxyresveratrol that may have more effective antioxidant properties. We synthesized a stilbene analog referred to as Compound 1 (2',3,4',5-tetramethoxystilbene); a benzamide analog referred to as Compound 2 ((2,4-dimethoxyphenyl)-3,5-dimethoxybenzamide); and three imine analogs referred to as Compound 3 (3,5-dimethoxybenzylidene)-(2,4-dimethoxyphenylamine), Compound 4 ((4-methoxybenzylidene)-(3-methoxyphenyl)amine), and Compound 5 ((4-methoxybenzylidene)phenylamine). The cytoprotective effects of these compounds were subsequently evaluated using hydrogen peroxide-treated PC12 cells. The cytoprotective effects of the imine analogs were greater than the effects of oxyresveratrol and the other analogs at concentrations of 200 µM. The Compound 3, which is the most effective imine analog of oxyresveratrol, exhibited these cytoprotective effects against hydrogen peroxide-induced oxidative stress through the regulation of heme oxygenase-1 (HO-1) expression and the translocation of nuclear factor E2-related factor 2 (Nrf2). Our results suggest that imine analogs of oxyresveratrol may be useful agents in reducing neuronal oxidative damage.

Identification of the G143A mutation associated with QoI resistance in Cercospora beticola field isolates from Michigan, United States.

BACKGROUND: Cercospora leaf spot (CLS), caused by the fungus Cercospora beticola, is the most serious foliar disease of sugar beet (Beta vulgaris L.) worldwide. Disease control is mainly achieved by timely fungicide applications. In 2011, CLS control failures were reported in spite of application of quinone outside inhibitor (QoI) fungicide in several counties in Michigan, United States. The purpose of this study was to confirm the resistant phenotype and identify the molecular basis for QoI resistance of Michigan C. beticola isolates. RESULTS: Isolates collected in Michigan in 1998 and 1999 that had no previous exposure to the QoI fungicides trifloxystrobin or pyraclostrobin exhibited QoI EC(50) values of ≤ 0.006 µg mL(-1) . In contrast, all isolates obtained in 2011 exhibited EC(50) values of > 0.92 µg mL(-1) to both fungicides and harbored a mutation in cytochrome b (cytb) that led to an amino acid exchange from glycine to alanine at position 143 (G143A) compared with baseline QoI-sensitive isolates. Microsatellite analysis of the isolates suggested that QoI resistance emerged independently in multiple genotypic backgrounds at multiple locations. A real-time PCR assay utilizing dual-labeled fluorogenic probes was developed to detect and differentiate QoI-resistant isolates harboring the G143A mutation from sensitive isolates. CONCLUSION: The G143A mutation in cytb is associated with QoI resistance in C. beticola. Accurate monitoring of this mutation will be essential for fungicide resistance management in this pathosystem.

Hypnotic profile of imines from benzimidazole chalcones: mechanism of synthesis, DFT studies and in silico screening.

A series of 1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene] amino}-1,3,4-thiadiazole-2- thiols (6a-6f) were synthesized by the acid catalyzed nucleophilic addition reaction between 1-(1H-benzimidazol-2-yl)-3- phenylprop-2-en-1-ones (4a-4f) and 5-amino-1,3,4-thiadiazole-2-thiol. All the synthesized compounds were characterised by IR, (1)HNMR, (13)CNMR, Mass and elemental analyses. A transition state calculation obtained from DFT study to explore the molecular mechanism of action of the synthetic route. The mechanism of synthesis revealed that the imidazole system can make an increase in the electrophilic character of carbonyl carbon in the benzimidazole chalcones. So the electron deficient carbonyl carbon could be efficiently attacked on the amino group of 1,3,4-thiadiazole ring to forms an imine linkage between the two heterocyclic systems. All the titled derivatives at a dose level of 10mg/kg body weight potentiate the hypnotic action of Phenobarbitone (at a dose of 10mg/kg body weight i.p.). The compounds such as 6b, 6a, and 6c showed a significant percentage increase in sleeping time relative to the control experiment 423.8, 387.6 and 329.5 respectively. The preclinical evaluation of the compounds was ascertained by blood-brain barrier, human oral absorption prediction and in silico toxicity assessment.

Genistein stimulates jejunal chloride secretion via sex-dependent, estrogen receptor or adenylate cyclase mechanisms.

BACKGROUND/AIMS: Daily subcutaneous injections with the phytoestrogen genistein, 600 mg/ kg genistein/day (600G) significantly increased intestinal chloride (Cl(-)) secretion (I(sc), µA/cm(2)) in C57BL/6J female and male murine jejunum after 1-2-weeks treatment. METHODS AND RESULTS: In 600G females, basolateral application of the adenylate cyclase inhibitor MDL-12330A (10 µM) significantly reduced basal and total I(sc) in the presence of forskolin (27 and 40% respectively, P < 0.05), with no effect in 600G males, suggesting that 600G-mediated increases in I(sc) in females are due to an adenylate cyclase-dependent mechanism. Concomitant injections with the non-selective estrogen receptor (ER) antagonist ICI-182780 (25 mg/kg/day) resulted in a significant inhibition of basal I(sc) in males (38%, P < 0.05), but was without effect in females (further reinforcing an ER-independent mechanism of action). The ERα-selective antagonist (MPP, 25 mg/kg/day) similarly significantly inhibited the basal I(sc) (37%, P < 0.05) in males, whereas the ERß-selective antagonist (PHTPP, 25 mg/kg/day) was without effect, suggesting that 600G-mediated increases in I (sc) in male mice are due to an ERα-dependent mechanism. Jejunum ERα/actin expression was significantly increased by 600G in males. Compared to intact mice, orchiectomy has differing effects on 600G-mediated basal Isc; castration (CAST) abolished the 600G-mediated increases in I(sc), and ovariectomy (OVX) had no effect on the 600G-stimulated increases in I(sc). Daily estradiol injections (10-20 mg/kg body weight estradiol (10E2 or 20E2) had no effect in intact females, whereas 10E2 significantly increased basal I(sc) in OVX females. CONCLUSION: These data suggest that daily estradiol and genistein injections have differential sex-dependent mechanisms of action on murine intestinal Cl(-) secretion.

Fluorous iminoalditols: a new family of glycosidase inhibitors and pharmacological chaperones.

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N-substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D-galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D-galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.

Effects of scoparone on dopamine release in PC12 cells.

The effects of scoparone on dopamine release in PC12 cells were investigated. Scoparone at 50-200 microM increased dopamine release into the culture medium. However, the released levels of dopamine by scoparone were not altered in the absence of extracellular Ca(2+) and by adenylyl cyclase inhibitor MDL-12,330A. Scoparone increased phosphorylation of PKA, CaMK II and synapsin I. Scoparone also enhanced K(+)-induced levels of dopamine release by CaMK II phosphorylation. These results suggest that scoparone increases dopamine release by synapsin I phosphorylation via activation of PKA and CaMK II, which are mediated by cyclic AMP levels and Ca(2+) influx.

Synthesis and insect attractant activity of fluorine-containing Pinus diterpenic amides and imines.

A series of fluorine-containing Pinus diterpenic amides and imines have been synthesised and their structures were confirmed by elemental analysis, IR, (1)H NMR spectroscopy and single crystal X-ray diffraction. Their insect attractant activity to Spodoptera litura were screened by leaf plate method; the results indicated that most fluorine-containing dehydroabietic amides and imines exhibited attractive activity to S. litura, in which dehydroabietic p-trifluoromethyl amide (A6) exhibit seven times the attractive rate compared with blank at the concentration of 0.01 g mL(-1). The fluorine moiety fused to the benzene ring results in decreased attractive rates for amides except (A6), while the effects of fluorine result in increased attractive rates for diterpenic imines.

pH-dependent Fe (II) pathophysiology and protective effect of an organoselenium compound.

Influence of pH on the extent of lipid peroxidation and the anti-oxidant potential of an organoselenium compound is explored. Acidosis increased the rate of lipid peroxidation both in the absence and presence of Fe (II) in rat's brain, kidney and liver homogenate and phospholipids extract from egg yolk. The organoselenium compound significantly protected lipids from peroxidation, both in the absence and presence of Fe (II). Changing the pH of the reaction medium did not alter the anti-oxidant activity of the tested compound. This study provides in vitro evidence for acidosis-induced oxidative stress in brain, kidney, liver homogenate and phospholipids extract and the anti-oxidant action of the tested organoselenium compound.

Syntheses and anti-depressant activity of 5-amino-1, 3, 4-thiadiazole-2-thiol imines and thiobenzyl derivatives.

A number of new imine derivatives of 5-amino-1, 3, 4-thiadiazole-2-thiol have been synthesized, and their anti-depressant activity was tested using imipramine as reference drug. Two compounds namely 5-{[1-(4-chlorophenyl)-3-(4-methoxy-phenyl)prop-2-en-1-ylidene]-amino}-5-benzylthio-1, 3,4 -thiadiazole 4i(b) and 5-{[1-(4-chlorophenyl)-3-(4-dimethyl-aminophenyl)-prop-2-en-1-ylidene]amino}-5-benzylthio-1,3,4-thiadiazole 4i(c) have shown significant anti-depressant activity, which decreased immobility time by 77.99% and 76.26% compared to the standard imipramine (82%). All the compounds in the series have passed neurotoxicity tests.

Synthesis and in vitro evaluation of 5-arylidene-3-hydroxyalkyl-2-phenylimino-4-thiazolidinones with antidegenerative activity on human chondrocyte cultures.

5-Arylidene-3-hydroxyalkyl-2-phenylimino-4-thiazolidinones (7,8) were synthesized and evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1beta. This in vitro model has proven to be a useful experimental model to reproduce the mechanisms involved in arthritic diseases. The cell viability, the amount of GAGs, the production of NO and PGE(2) and the inhibition of MMP-3 were measured. Several thiazolidinones 7 and 8 exhibited the ability to block the production or action of the degenerative factors induced by IL-1beta.

Zwitterionic glycosidase inhibitors: salacinol and related analogues.

Natural products with interesting biological properties and structural diversity have often served as valuable lead drug candidates for the treatment of human diseases. Salacinol, a naturally occurring alpha-glucosidase inhibitor, was shown to be one of the active principles of the aqueous extract of a medicinal plant that has been prescribed traditionally as an Ayurvedic treatment for type II diabetes. Salacinol contains an intriguing zwitterionic sulfonium-sulfate structure that comprises a 1,4-anhydro-4-thio-D-arabinitol core and a polyhydroxylated acyclic chain. Due to the unique structural features and its potential to become a lead drug candidate in the treatment of type II diabetes, a great deal of attention has been focused on salacinol and its analogues. Since the isolation of salacinol, several papers describing various synthetic routes to salacinol and its analogues have appeared in the literature. This review is aimed at highlighting the synthetic aspects of salacinol and related compounds as well as their structure-activity relationship studies.