Highly efficient bioconversion of icariin to icaritin by whole-cell catalysis.

BACKGROUND: Icaritin is an aglycone of flavonoid glycosides from Herba Epimedii. It has good performance in the treatment of hepatocellular carcinoma in clinical trials. However, the natural icaritin content of Herba Epimedii is very low. At present, the icaritin is mainly prepared from flavonoid glycosides by α-L-rhamnosidases and ß-glucosidases in two-step catalysis process. However, one-pot icaritin production required reported enzymes to be immobilized or bifunctional enzymes to hydrolyze substrate with long reaction time, which caused complicated operations and high costs. To improve the production efficiency and reduce costs, we explored α-L-rhamnosidase SPRHA2 and ß-glucosidase PBGL to directly hydrolyze icariin to icaritin in one-pot, and developed the whole-cell catalytic method for efficient icaritin production. RESULTS: The SPRHA2 and PBGL were expressed in Escherichia coli, respectively. One-pot production of icaritin was achieved by co-catalysis of SPRHA2 and PBGL. Moreover, whole-cell catalysis was developed for icariin hydrolysis. The mixture of SPRHA2 cells and PBGL cells transformed 200 g/L icariin into 103.69 g/L icaritin (yield 95.23%) in 4 h in whole-cell catalysis under the optimized reaction conditions. In order to further increase the production efficiency and simplify operations, we also constructed recombinant E. coli strains that co-expressed SPRHA2 and PBGL. Crude icariin extracts were also efficiently hydrolyzed by the whole-cell catalytic system. CONCLUSIONS: Compared to previous reports on icaritin production, in this study, whole-cell catalysis showed higher production efficiency of icaritin. This study provides promising approach for industrial production of icaritin in the future.

Discovery of natural 15-LOX small molecule inhibitors from Chinese herbal medicine using virtual Screening, biological evaluation and molecular dynamics studies.

Chinese herbal medicines (CHM) are frequently used to treat different types of inflammatory diseases and 15-Lipoxygenase (15-LOX) is a critical target enzyme for treating various inflammatory diseases. In this study, natural 15-LOX inhibitors were identified in CHM using an approach of virtual screening combined with the biological assays. First, an in-house Chinese medicine database containing 360 compounds was screened using a virtual screening approach based on pharmacophore and molecular docking to uncover several novel potential 15-LOX inhibitors. Secondly, the inhibitory effect of virtual screening hits against the 15-LOX enzyme was validated in an in vitro enzyme inhibition assay. Then, a tumor necrosis factor-α (TNF-α) release assay was carried out to explore the anti-inflammatory response of the active compounds. Furthermore, molecular dynamics (MD) simulation and binding free energy calculation were applied to analyze the process of inhibitors binding and also compared the mode of binding of the inhibitors by using the Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) method. Finally, licochalcone B and eriodictyol were confirmed as inhibitors of the 15-LOX enzyme with IC50 values of 9.67 and 18.99 µM, respectively. In vitro cell-based assay showed that licochalcone B and eriodictyol inhibited the release of TNF-α factor in RAW264.7 cells stimulated by lipopolysaccharides (LPS) in a dose-dependent manner. Molecular dynamics and binding free energy analysis showed that the two 15-LOX-ligand systems immediately attained equilibrium with almost 1 Å fluctuation, the calculated binding free energies were found around -18.89 and -12.96 kcal/mol for licochalcone B and eriodictyol, respectively. Thr412, Arg415, Val420, Thr429, Ile602 and Trp606 were the main amino acid residues for the inhibition of 15-LOX enzyme activity. The current study confirms that licochalcone B and eriodictyol are 15-LOX inhibitors and can suppress the release of the TNF-α factor in RAW264.7 cells stimulated by LPS, thus providing a basis for the follow-up research and development for 15-LOX inhibitors.

Norwogonin attenuates hypoxia-induced oxidative stress and apoptosis in PC12 cells.

BACKGROUND: Norwogonin is a natural flavone with three phenolic hydroxyl groups in skeletal structure and has excellent antioxidant activity. However, the neuroprotective effect of norwogonin remains unclear. Here, we investigated the protective capacity of norwogonin against oxidative damage elicited by hypoxia in PC12 cells. METHODS: The cell viability and apoptosis were examined by MTT assay and Annexin V-FITC/PI staining, respectively. Reactive oxygen species (ROS) content was measured using DCFH-DA assay. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and antioxidant enzyme levels were determined using commercial kits. The expression of related genes and proteins was measured by real-time quantitative PCR and Western blotting, respectively. RESULTS: We found that norwogonin alleviated hypoxia-induced injury in PC12 cells by increasing the cell viability, reducing LDH release, and ameliorating the changes of cell morphology. Norwogonin also acted as an antioxidant by scavenging ROS, reducing MDA production, maintaining the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and decreasing the expression levels of HIF-1α and VEGF. In addition, norwogonin prevented cell apoptosis via inhibiting the expression levels of caspase-3, cytochrome c and Bax, while increasing the expression levels of Bcl-2 and the ratio of Bcl-2/Bax. CONCLUSIONS: Norwogonin attenuates hypoxia-induced injury in PC12 cells by quenching ROS, maintaining the activities of antioxidant enzymes, and inhibiting mitochondrial apoptosis pathway.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis through Bcl-2/Bax Proteins Expression.

BACKGROUND: Deoxypodophyllotoxin, isolated from the Traditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant anti-tumor activity with strong toxicity in vitro and in vivo. OBJECTIVE: In this article, a series of deoxypodophyllotoxin derivatives were synthesized and their anti-tumor effectiveness was evaluated. METHODS: The anti-tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT assay method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. RESULTS: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29, and MG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. CONCLUSION: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Tanshinones and their Derivatives: Heterocyclic Ring-Fused Diterpenes of Biological Interest.

The available scientific literature regarding tanshinones is very abundant, and after its review, it is noticeable that most of the articles focus on the properties of tanshinone I, cryptotanshinone, tanshinone IIA, sodium tanshinone IIA sulfonate and the dried root extract of Salvia miltiorrhiza (Tan- Shen). However, although these products have demonstrated important biological properties in both in vitro and in vivo models, their poor solubility and bioavailability have limited their clinical applications. For these reasons, many studies have focused on the search for new pharmaceutical formulations for tanshinones, as well as the synthesis of new derivatives that improve their biological properties. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2015) on tanshinones in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we offer an update on the last five years of new research on these quinones, focusing on their synthesis, biological activity on noncommunicable diseases and drug delivery systems, to support future research on its clinical applications.

SP94 Peptide-Functionalized PEG-PLGA Nanoparticle Loading with Cryptotanshinone for Targeting Therapy of Hepatocellular Carcinoma.

To achieve improved drug delivery efficiency to hepatocellular carcinoma (HCC), biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP), surface-modified with SP94 peptide, were designed for the efficient delivery of cryptotanshinone to the tumor for the treatment of HCC. Cryptotanshinone NP and SP94-NP were prepared by using nanoprecipitation. The physicochemical and pharmaceutical properties of the NP and SP94-NP were characterized, and the release kinetics suggested that both NP and SP94-NP provided continuous, slow release of cryptotanshinone for 48 h. The in vitro cellular experiment demonstrated that SP94-NP significantly enhanced the cellular uptake of cryptotanshinone and induced high cytotoxicity and cellular apoptosis of hepatocellular carcinoma (HepG2) cells. The in vivo detecting results of targeting effect using the Cy5.5 probe evidenced that SP94-NP showed an accumulation in tumor more efficiently than that of unconjugated ones. Meanwhile, SP94-NP exhibited the smallest tumor size than other groups and showed no toxicity to body. The results of this study provide a promising nanoplatform for the targeting of HCC.

Associating 197 Chinese herbal medicine with drug targets and diseases using the similarity ensemble approach.

Chinese herbal medicine (CHM) addresses complex diseases through polypharmacological interactions. However, systematic studies of herbal medicine pharmacology remain challenging due to the complexity of CHM ingredients and their interactions with various targets. In this study, we aim to address this challenge with computational approaches. We investigated the herb-target-disease associations of 197 commonly prescribed CHMs using the similarity ensemble approach and DisGeNET database. We demonstrated that this method can be applied to associate herbs with their putative targets. In the case study of three well-known herbs, Radix Glycyrrhizae, Flos Lonicerae, and Rhizoma Coptidis, approximately 70% of the predicted targets were supported by scientific literature. By linking 406 targets to 2439 annotated diseases, we further analyzed the pharmacological functions of 197 herbs. Finally, we proposed a strategy of target-oriented herbal formula design and illustrated the target profiles for four common chronic diseases, namely, Alzheimer's disease, depressive disorder, hypertensive disease, and non-insulin-dependent diabetes mellitus. This computational approach holds great potential in the target identification of herbs, understanding the molecular mechanisms of CHM, and designing novel herbal formulas.

Study on evaluation of toxicology and quality control of Yimusake tablet.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yimusake tablet (YMSK-T) is a type of Xinjiang Uygur Medicine, which affects curing diseases of impotence and premature ejaculation. It has remarkable pharmacological effects that mainly involve improving the number and shape of smooth muscle cells in the corpus cavernosum and enhancing the relaxation and contraction function of corpus cavernosum smooth muscle. AIM OF THE STUDY: The YMSK-T prescription, which consists of 11 traditional herbs, has significant pharmacological effects, however the evaluation of toxicology and quality control of the preparation has not yet been reported. Therefore, in this study, we evaluated the toxicology and quality control of YMSK-T to ensure its safety and effectiveness in clinical applications. MATERIALS AND METHODS: Male rats were divided into three groups and were given continuous gavage administration of high, medium and low concentrations of YMSK-T. To determine hematopoietic parameters, orbital blood was collected at regular intervals. At termination of the experiment, rats were dissected for histopathological examination. According to the function of the prescription medicinal materials, seven active components were selected for content determination under the same chromatographic condition of using 0.2% aqueous phosphoric acid (solvent A) and acetonitrile (solvent B) with a 40 min post time: 0-13 min, 20% →30% B; 13-26 min, 30% →72% B; 26-38 min, 72% →92% B; 38-40 min, 92% →96% B. The column was maintained at 25 °C and the total sample injection was 10 µL. RESULTS: Our data showed that using a large dose (400X the dosage used in humans) of YMSK-T resulted in myocardium and liver damage, and eventually death of the rats. At sub-chronic toxicity, no significant differences were observed among indexes about relative organ weight, hematology, serum biochemistry and histopathological examination, and rats behaved normally. Our results also demonstrated that the YMSK-T dosage used was not toxic in the normal range. The linearity of each component was sufficient (correlation coefficients>0.9997). Moreover, the relative standard deviations of precision, repeatability, stability, and recovery were less than 2.0%, which showed that the method for determination of content was stable and reliable. CONCLUSIONS: YMSK-T has been found to be relatively safe in a rat model, and the method of content determination can be used for quality control of YMSK-T. Toxicology and quality control studies indicated that, the drug is safe and effective for clinical application.

Paeonol Derivatives and Pharmacological Activities: A Review of Recent Progress.

Paeonol, 2-hydroxy-4-methoxy acetophenone, is one of the main active ingredients of traditional Chinese medicine such as Cynanchum paniculatum, Paeonia suffruticosa Andr and Paeonia lactiflora Pall. Modern medical research has shown that paeonol has a wide range of pharmacological activities. In recent years, a large number of studies have been carried out on the structure modification of paeonol and the mechanism of action of paeonol derivatives has been studied. Some paeonol derivatives exhibit good pharmacological activities in terms of antibacterial, anti-inflammatory, antipyretic analgesic, antioxidant and other pharmacological effects. Herein, the research progress on paeonol derivatives and their pharmacological activities were systematically reviewed.

Chitosan Gels and Cryogels Cross-Linked with Diglycidyl Ethers of Ethylene Glycol and Polyethylene Glycol in Acidic Media.

Here we show that the efficacy of the chitosan interaction with diglycidyl ethers of glycols significantly depends on pH and the nature of acid used to dissolve chitosan. In solutions of hydrochloric acid, cross-linking with diglycidyl ethers of ethylene glycol (EGDGE) and polyethylene glycol (PEGDGE) at room and subzero temperatures yields mechanically stable chitosan gels and cryogels, while in acetic acid solutions only weak chitosan gels can be formed under the same conditions. A combination of elemental analysis, FT-IR spectroscopy, and solid state 13C and 15N NMR spectroscopy was used to elucidate possible differences in the mechanism of chitosan cross-linking in alkaline and acidic media at room and subzero temperatures. We have proved that in acidic media diglycidyl ethers of glycols interacted with chitosan mainly via hydroxyl groups at the C6 position of the glucosamine unit. Besides, not only cross-linkages but also grafts were formed at room temperature. The cryo-concentration effect facilitates cross-linkages formation at -10 °C and, despite lower modification degrees compared to those of gels obtained at room temperature, supermacroporous chitosan cryogels with Young's moduli up to 90 kPa can be fabricated in one step. Investigations of chitosan cryogels biocompatibility in a mouse model have shown that a moderate inflammatory reaction around the implants is accompanied by formation of a normal granulation tissue. No toxic, immunosuppressive, and sensitizing effects on the recipient's tissues have been observed.

Synthesis and evaluation of the antiproliferative efficacy of BRM270 phytocomposite nanoparticles against human hepatoma cancer cell lines.

BRM270 is the most leading phytochemical extract that possesses potent anticancer properties. A major challenge associated with this drug is its low bioavailability and thus requires high dosages for cancer treatment. Here, we report the novel nano-synthesis of phyto-composite, BRM270 for the first time by mechanical milling method with specific modifications for enhanced cytotoxicity against HepG2 human hepatoma cancer cells. Unlike free BRM270 and other phytomedicines, BRM270 nanoparticles (BRM270 NPs) are well-dispersed and small sized (23 to 70 nm) which is believed to greatly enhanced cellular uptake. Furthermore, the acidic tumor microenvironment attracts BRM270 NPs enhancing targeted therapy while leaving normal cells less affected. The comparative cytotoxicity analysis using MTT assay among the three treatment groups, such as free BRM270, BRM270 NPs, and doxorubicin demonstrated that BRM270 NPs induced greater cytotoxicity against HepG2 cells with an effective drug concentration of 12 µg/ml. From FACS analysis, we observed an apoptotic cell death of 44.4% at BRM270 NPs treated cells while only 12.5% found in the free BRM270 treated cells. Further, the comparative relative expression profiling of the candidate genes were showed significant (p < 0.05) down-regulation of IL6, BCL2, p53, and MMP9 in the BRM270 NPs treated cells, compared to the free BRM270 and doxorubicin. Indeed, the genes, CASPASE 9 and BAX have shown significant (p < 0.05) upregulation in cells treated with BRM270 NPs as compared to counter treatment groups. The investigation of the signal pathways and protein-protein network associations were also carried out to elucidate the functional insights underlying anti-cancer potential of BRM270 NPs in HepG2 cells. Taken together, our findings demonstrated that these uniquely engineered BRM270 NPs effectively enter into the cancer cells due to its acidic microenvironment thereby inducing apoptosis and regulate the cell-proliferation in-vitro at extremely low dosages.

Systems pharmacology reveals the unique mechanism features of Shenzhu Capsule for treatment of ulcerative colitis in comparison with synthetic drugs.

In clinic, both synthetic drugs and Shenzhu Capsule (SZC), one kind of traditional Chinese medicines (TCMs), are used to treat ulcerative colitis (UC). In our study, a systems pharmacology approach was employed to elucidate the chemical and mechanism differences between SZC and synthetic drugs in treating UC. First, the compound databases were constructed for SZC and synthetic drugs. Then, the targets of SZC were predicted with on-line tools and validated using molecular docking method. Finally, chemical space, targets, and pathways of SZC and synthetic drugs were compared. Results showed that atractylenolide I, atractylone, kaempferol, etc., were bioactive compounds of SZC. Comparison of SZC and synthetic drugs showed that (1) in chemical space, the area of SZC encompasses the area of synthetic drugs; (2) SZC can act on more targets and pathways than synthetic drugs; (3) SZC can not only regulate immune and inflammatory reactions but also act on ulcerative colitis complications (bloody diarrhea) and prevent UC to develop into colorectal cancer whereas synthetic drugs mainly regulate immune and inflammatory reactions. Our study could help us to understand the compound and mechanism differences between TCM and synthetic drugs.

Discovery of traditional Chinese medicine monomers and their synthetic intermediates, analogs or derivatives for battling P-gp-mediated multi-drug resistance.

P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) is a well-documented and predominant phenotype hampering patients' response to cancer chemotherapy. Although the past several decades have witnessed the development of three generations of P-gp inhibitors, they have not lived up to the high expectations owing to their drawbacks, as exemplified by limited efficacy, drug-drug interactions (DDIs) and severe untoward reactions. The discovery of artemisinin is a testimony of the importance of traditional Chinese medicine (TCM) in innovative drug discovery. In search for a new generation of chemo-sensitizers, P-gp modulators originated from TCM have attracted increasing concern in the research community. In addition to identify TCM monomers or their synthetic intermediates as P-gp modulators, massive medicinal chemistry efforts have been made in discovering promising structural analogs and derivatives of them. Among these, compounds with dual role both as P-gp inhibitor and cytotoxic agent have continuously emerged. Hence, in this article, we will mainly enumerate the representative work conducted in the discovery of TCM monomers and their synthetic intermediates, analogs or derivatives as reversers of P-gp-mediated MDR.

Synthesis and evaluation of panaxatriol derivatives as Na+, K+-ATPase inhibitors.

Panaxatriol, a triterpene bearing a steroid-like structure similar to cardiac glycosides, was presumed to share the same bioactivity with cardiac glycosides, and may be a potential Na+, K+-ATPase inhibitor. In this paper, a series of panaxatriol derivatives were synthesized and evaluated for Na+, K+-ATPase inhibitory activities. The results of biological tests showed that more than half of the synthesized derivatives presented increased inhibitory activities compared with panaxatriol. Of these compounds, 13a with a 3, 4-seco skeleton showed the most potent inhibitory activity, which was equal to that of the standard drug digoxin. To understand the binding mode of the most active compound, molecular docking study of 13a with Na+, K+-ATPase was conducted. Therefore, 13a may serve as a new lead compound for the development of novel Na+, K+-ATPase inhibitors.

Synthesis and antioxidant properties of Lycium barbarum polysaccharides capped selenium nanoparticles using tea extract.

Selenium nanoparticles (SeNPs) have attracted increasing interest over the last decades because of their activities on redox balance in human body. However, the SeNPs tend to aggregate into large clusters, resulting in lower bioactivity, bioavailability and biocompatibility. Surface-capping agents on SeNPs play crucial roles in its stabilization and biological activity. Here, a green synthesis method for the preparation of Lycium barbarum polysaccharides capped SeNPs using green tea extracts as reductants under mild conditions, at room temperature, is reported. The structure, size, morphology and thermal behaviour were analyzed by various characterization techniques. The functionalized nanoparticles demonstrated high antioxidant activity, including DPPH and ABTS free radical scavenging. Moreover, the SeNPs significantly protected the H2O2-induced PC-12 cell death. Taken together, these results evidence the possible application of these SeNPs as antioxidants food supplement or ingredient and neuroprotective agent.

Preparation and Characterization of Copolymer Micelles for the Solubilization and In Vitro Release of Luteolin and Luteoloside.

Luteolin (LUT) and luteoloside (LUS) belong to flavonoids with high anticancer potential and were loaded into biodegradable diblock copolymer micelles of methoxy polyethylene glycol-polycaprolactone (mPEG5K-PCL10K), methoxy polyethylene glycol-polylactide-co-glycolide (mPEG5K-PLGA10K), and methoxy polyethylene glycol-polylactide (mPEG5K-PDLLA10K) by a self-assembly method, creating water-soluble LUT and LUS copolymer micelles, respectively. The solubilization formulations of the copolymer micelles were optimized with response surface methodology (RSM). The obtained drug micelles are torispherical under transmission electron microscope (TEM) with an average diameter of about 70 nm. The mPEG5K-PLGA10K exhibited higher loading capacity for LUS which was 4.33%, and LUT- (or LUS)-loaded mPEG5K-PCL10K exhibited a better stability and encapsulation efficiency which was 65.1 and 55.8%, respectively. The in vitro drug release study showed above 47% of LUT was released from micelles at pH 7.4 PBS; however, no more than 35% of LUT was released at pH 6.4 PBS within 24 h. Meanwhile, no more than 30% of LUS was released from micelles whether at pH 6.4 or 7.4 PBS solution within 24 h.

A Polysaccharide Isolated from Mycelia of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) Induced Apoptosis in Precancerous Human Gastric Cells.

Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.

Ganoderma neo-japonicum Imazeki revisited: Domestication study and antioxidant properties of its basidiocarps and mycelia.

Mushroom cultivation benefits humankind as it deliberately encourages wild mushrooms to be commercially propagated while recycling agricultural wastes. Ganoderma neo-japonicum is a rare polypore mushroom found growing on decaying Schizostachyum brachycladium (a tropical bamboo) clumps in Malaysia. The Malaysian indigenous tribes including the Temuans and Temiars use the basidiocarps of G. neo-japonicum to treat various ailments including diabetes. In this study, the domestication of G. neo-japonicum in artificial logs of different agricultural residues was investigated. Sawdust promoted the mycelia spawn colonisation in the shortest period of 38 ± 0.5 days. However, only sawdust and bamboo dust supported the primodia formation. Complex medium supported mycelium growth in submerged cultures and 27.11 ± 0.43 g/L of mycelia was obtained after 2 weeks of cultivation at 28 °C and 200 rpm. Antioxidant potential in mushroom may be influenced by different cultivation and extraction methods. The different extracts from the wild and cultivated basidiocarps as well as mycelia were then tested for their antioxidant properties. Aqueous and ethanol extracts of mycelia and basidiocarps tested had varying levels of antioxidant activities. To conclude, domestication of wild G. neo-japonicum using agroresidues may ensure a continuous supply of G. neo-japonicum for its medicinal use while ensuring the conservation of this rare species.

Pharmacological importance of optically active tetrahydro-ß-carbolines and synthetic approaches to create the C1 stereocenter.

1,2,3,4-Tetrahydro-ß-carbolines (THßCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THßCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly summarizes the methods to obtain the C1 stereocenter and concentrates on evaluating the pharmacological importance of optically active C1-substituted THßCs, including their PDE5-inhibitory, antimalarial, antiviral and antitumor activities.

Synthesis of 6-deoxymollugins and their inhibitory activities on tyrosinase.

A series of 6-deoxymollugins were prepared five steps from benzaldehyde and its derivatives via phenylboronic acid-catalyzed chromenylation as a key step. Their inhibitory activities against tyrosinase from mushroom were evaluated to show that the parent, methyl 2,2-dimethyl-2H-benzo[h]chromene-5-carboxylate (9a) showed best and promising inhibitory activity at IC50 = 18.3 µM.