Utilization of vanillin to prepare sulfated Calix[4]resorcinarene as efficient organocatalyst for biodiesel production based on methylation of palmitic acid and oleic acid.

Recently, biodiesel production from palm oils has been thoroughly investigated to substitute crude oil due to its scarcity. However, the biodiesel production process is time-consuming due to its slow kinetics; thus, concentrated sulfuric acid has been used to fasten the reaction process in some industries. Unfortunately, sulfuric acid is a toxic, corrosive, and non-environmentally friendly catalyst. In this study, we prepared sulfated Calix[4]resorcinarene derived from vanillin as an efficient organocatalyst to replace sulfuric acid. The catalytic activity of sulfated Calix[4]resorcinarenes was evaluated through the methylation of palmitic acid and oleic acid as model compounds due to their abundant amounts in palm oil. The Calix[4]resorcinarene and sulfated Calix[4]resorcinarenes have been obtained through a one-pot reaction in 71.8-98.3% yield. Their chemical structures were confirmed by using FTIR, NMR and HRMS spectrometry analyses. The results showed that the sulfated Calix[4]resorcinarene exhibited high catalytic activity for methyl palmitate and methyl oleate productions in 94.8 ± 1.8 and 97.3 ± 2.1% yield, respectively, which was comparable to sulfuric acid (96.3 ± 1.8 and 95.9 ± 2.5%). The optimum condition was achieved by using 0.020 wt equivalent of organocatalyst for 6 h reaction process at 338 K. The methylation of palmitic acid and oleic acid fits well with the first-order kinetic model (R2 = 0.9940-0.9999) with a reaction rate constant of 0.6055 and 1.1403 h-1, respectively. Further investigation reveals that the hydroxyl group of vanillin plays a pivotal role in the organocatalytic activity of sulfated Calix[4]resorcinarene.

New Report: Genome Mining Untaps the Antibiotics Biosynthetic Gene Cluster of Pseudoalteromonas xiamenensis STKMTI.2 from a Mangrove Soil Sediment.

The marine bacterium Pseudoalteromonas xiamenensis STKMTI.2 was isolated from a mangrove soil sediment on Setokok Island, Batam, Indonesia. The genome of this bacterium consisted of 4,563,326 bp (GC content: 43.2%) with 1 chromosome, 2 circular plasmids, 2 linear plasmids, 4,824 protein-coding sequences, 25 rRNAs, 104 tRNAs, 4 ncRNAs, and 1 clustered, regularly interspaced, short palindromic repeated (CRISPR). This strain possessed cluster genes which are responsible for the production of brominated marine pyrroles/phenols (bmp), namely, bmp8 and bmp9. Other gene clusters responsible for the synthesis of secondary metabolites were identified using antiSMASH and BAGEL4, which yielded five results, namely, non-ribosomal peptides, polyketide-like butyrolactone, Lant class I, and RiPP-like, detected in chromosome 1, while prodigiosin was detected in the unnamed plasmid 5. This suggests that these whole genome data will be of remarkable importance for the improved understanding of the biosynthesis of industrially important bioactive and antibacterial compounds produced by P. xiamenensis STKMTI.2.

Synthesis and in vitro assay of hydroxyxanthones as antioxidant and anticancer agents.

In the present work, three hydroxyxanthones were synthesized in 11.15-33.42% yield from 2,6-dihydroxybenzoic acid as the starting material. The chemical structures of prepared hydroxyxanthones have been elucidated by using spectroscopic techniques. Afterward, the hydroxyxanthones were evaluated as antioxidant agents through radical scavenging assay; and anticancer agents through in vitro assays against WiDr, MCF-7, and HeLa cancer cell lines. Hydroxyxanthone 3b was categorized as a strong antioxidant agent (IC50 = 349 ± 68 µM), while the other compounds were categorized as moderate antioxidant agents (IC50 > 500 µM). On the other hand, hydroxyxanthone 3a exhibited the highest anticancer activity (IC50 = 184 ± 15 µM) and the highest selectivity (SI = 18.42) against MCF-7 cancer cells. From the molecular docking study, it was found that hydroxyxanthone 3a interacted with the active sites of Topoisomerase II protein through Hydrogen bonding with DG13 and π-π stacking interactions with DA12 and DC8. These findings revealed that hydroxyxanthones are potential candidates to be developed as antioxidant and anticancer agents in the future.

Synthesis and Evaluation of Chalcone Derivatives as Novel Sunscreen Agent.

Ultraviolet (UV) irradiation is a serious problem for skin health thus the interest in the research to develop sunscreen agent has been increasing. Chalcone is a promising compound to be developed as its chromophore absorbs in the UV region. Therefore, in the present work, we synthesized eight chalcone derivatives through Claisen-Schmidt condensation at room temperature. The evaluation of the optical properties of each chalcone derivatives in the UV region was conducted through spectroscopic and computational studies. The synthesized chalcones were obtained in good yields and they were active in the UV region. The results revealed that more methoxy substituents to chalcone leads toward red shift. All chalcone derivatives have high molar absorptivity value (21,000-56,000) demonstrating that they have the potential to be used as the sunscreen agent. The cytotoxicity assay showed that chalcone derivatives were demonstrating low toxicity toward normal human fibroblast cell, which is remarkable. Therefore, we concluded that the synthesized chalcones in this work were potential to be developed as novel sunscreen agents in real application.

In Vitro Antiplasmodial, Heme Polymerization, and Cytotoxicity of Hydroxyxanthone Derivatives.

The previous study showed that xanthone had antiplasmodial activity. Xanthone, with additional hydroxyl groups, was synthesized to increase its antiplasmodial activity. One of the strategies to evaluate a compound that can be developed into an antimalarial drug is by testing its mechanism in inhibiting heme polymerization. In acidic condition, hematin can be polymerized to ß-hematin in vitro, which is analog with hemozoin in Plasmodium. This study was conducted to evaluate the antiplasmodial activity of hydroxyxanthone derivative compounds on two strains of Plasmodium falciparum 3D-7 and FCR-3, to assess inhibition of heme polymerization activity and determine the selectivity of hydroxyxanthone derivative compounds. The antiplasmodial activity of each compound was tested on Plasmodium falciparum 3D-7 and FCR-3 with 72 hours incubation period, triplicated in three replications with the microscopic method. The compound that showed the best antiplasmodial activity underwent flow cytometry assay. Heme polymerization inhibition test was performed using the in vitro heme polymerization inhibition activity (HPIA) assay. The antiplasmodial activity and heme polymerization inhibition activity were expressed as the 50% inhibitory concentration (IC50). In vitro cytotoxicity was tested using the MTT assay method on Vero cell lines to determine its selectivity index. The results showed that among 5-hydroxyxanthone derivative compounds, the 1,6,8-trihydroxyxanthone had the best in vitro antiplasmodial activity on both 3D-7 and FCR-3 Plasmodium falciparum strains with IC50 values of 6.10 ± 2.01 and 6.76 ± 2.38 µM, respectively. The 1,6,8-trihydroxyxanthone showed inhibition activity of heme polymerization with IC50 value of 2.854 mM and showed the high selectivity with selectivity index of 502.2-556.54. In conclusion, among 5-hydroxyxanthone derivatives tested, the 1,6,8-trihydroxyxantone showed the best antiplasmodial activity and has heme polymerization inhibition activity and high selectivity.

Synergistic Effect of 1,3,6-Trihydroxy-4,5,7-Trichloroxanthone in Combination with Doxorubicin on B-Cell Lymphoma Cells and Its Mechanism of Action Through Molecular Docking.

BACKGROUND: The increasing rate of cancer chemoresistance and adverse side effects of therapy have led to the wide use of various chemotherapeutic combinations in cancer management, including lymphoid malignancy. OBJECTIVE: We investigated the effects of a combination of 1,3,6-trihydroxy-4,5,7-trichloroxanthone (TTX) and doxorubicin on the Raji lymphoma cell line. METHODS: Raji cells were treated with different concentrations of TTX, doxorubicin, or combinations thereof. Cancer cell growth inhibition was evaluated using 3-(4,5-dimethyltiazol-2-yl)-2,5- diphenyltetrazolium bromide/MTT assay to determine the half-maximal inhibitory concentration. Combination index values were calculated using CompuSyn (ComboSyn, Inc, Paramus, NJ). Molecular docking was conducted using a Protein-Ligand ANT System. RESULTS: The mean (SD) half-maximal inhibitory concentration values of TTX and doxorubicin were 15.948 (3.101) µM and 25.432 (1.417) µM, respectively. The combination index values of the different combinations ranged from 0.057 to 0.285, indicating strong to very strong synergistic effects. The docking study results reveal that TTX docks at the active site of Raf-1 and c-Jun N-kinase receptors with predicted free energies of binding of -79.37 and -75.42 kcal/mol, respectively. CONCLUSIONS: The xanthone-doxorubicin combination showed promising in vitro activity against lymphoma cells. The results also indicate that the TTX and doxorubicin combination's effect was due to the interaction between TTX with Raf-1 and c-Jun N-kinase receptors, 2 determinants of doxorubicin resistance progression.

Antibacterial and Antifungal Activity of Three Monosaccharide Monomyristate Derivatives.

Microbial infections remains a serious challenge in food industries due to their resistance to some of the well-known antibacterial and antifungal agents. In this work, a novel monomyristoyl ester (fructosyl monomyristate) and two other derivatives (i.e., glucosyl and galactosyl monomyristates) were successfully synthesized from myristic acid and monosaccharides in two-step reactions. First, the myristic acid was converted to myristoyl chloride, and then the myristoyl chloride was reacted with fructose, glucose and galactose separately to produce the corresponding monosaccharide monomyristate derivatives. The structures of the synthesized products were confirmed by Fourier transform infrared (FTIR), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR), and mass spectral (MS) data. The monomyristates esters were obtained in reaction yields of 45.80%-79.49%. The esters were then evaluated for their antimicrobial activity using the disc diffusion test. It was found that the esters exhibited a medium antibacterial activity against gram-positive bacteria; however, they showed a weak antibacterial activity against gram-negative bacteria. Amongst the esters, galactosyl myristate yielded the highest antibacterial activity against Salmonella typhimurium, Staphylococcus aureus and Bacillus subtilis, while glucosyl monomyristate exhibited the highest antibacterial activity only against Escherichia coli. Additionally, all products showed remarkable antifungal activity against Candida albicans. These findings demonstrate that monosaccharide monomyristate derivatives are promising for use as biocompatible antimicrobial agents in the future.

Preparation of Monoacylglycerol Derivatives from Indonesian Edible Oil and Their Antimicrobial Assay against Staphylococcus aureus and Escherichia coli.

In the present work, linoleic acid and oleic acid were isolated from Indonesian corn oil and palm oil and they were used to prepare monoacylglycerol derivatives as the antibacterial agent. Indonesian corn oil contains 57.74% linoleic acid, 19.88% palmitic acid, 11.84% oleic acid and 3.02% stearic acid. While Indonesian palm oil contains 44.72% oleic acid, 39.28% palmitic acid, 4.56% stearic acid and 1.54% myristic acid. The oleic acid was purified by using Urea Inclusion Complex (UIC) method and its purity was significantly increased from 44.72% to 94.71%. Meanwhile, with the UIC method, the purity of ethyl linoleate was increased from 57.74% to 72.14%. 1-Monolinolein and 2-monoolein compounds were synthesized via two-step process from the isolated linoleic acid and oleic acid, respectively. The preliminary antibacterial assay shows that the 1-monolinolein did not give any antibacterial activity against Staphylococcus aureus and Escherichia coli, while 2-monoolein showed weak antibacterial activity against Staphylococcus aureus.

Biological activity, quantitative structure-activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs.

BACKGROUND: Xanthone derivatives have a wide range of pharmacological activities, such as those involving antibacterial, antiviral, antimalarial, anthelmintic, anti-inflammatory, antiprotozoal, and anticancer properties. Among these, we investigated the anticancer properties of xanthone. This research aimed to analyze the biological activity of ten novel xanthone derivatives, to investigate the most contributing-descriptors for their cytotoxic activities, and to examine the possible mechanism of actions of xanthone compound through molecular docking. MATERIALS AND METHODS: The cytotoxic tests were carried out on WiDR and Vero cell lines, by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay method. The structural features required for xanthone's anticancer activity were conducted by using the semi-empirical Austin Model-1 method, and continued with quantitative structure-activity relationship (QSAR) analysis using BuildQSAR program. The study of the possible mechanism of actions of the selected xanthone compound was done through molecular docking with PLANTS. RESULTS: The three novel xanthone derivatives (compounds 5, 7, and 8) exhibited cytotoxic activity with compound 5 showed the highest degree of cytotoxicity at concentration 9.23 µg/mL (37.8 µM). The following best equation model was obtained from the BuildQSAR calculation: log 1/IC50 = -8.124 qC1 -35.088 qC2 -6.008 qC3 + 1.831 u + 0.540 logP -9.115 (n = 10, r = 0.976, s = 0.144, F = 15.920, Q2 = 0.651, SPRESS = 0.390). This equation model generated 15 proposed new xanthone compounds with better-predicted anticancer activities. A molecular docking study of compound 5 showed that xanthone formed binding interactions with some receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation (COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor. CONCLUSION: The results suggested that compound 5 showed the best cytotoxic activity among the xanthone derivatives tested. QSAR analysis showed that the descriptors contributed to xanthone's cytotoxic activity were the net atomic charge at qC1, qC2, and qC3 positions, also dipole moment and logP. Compound 5 was suspected to be cytotoxic by its inhibition of telomerase, COX-2, and CDK2 receptors.

In Vitro Antifungal Activity of (1)-N-2-Methoxybenzyl-1,10-phenanthrolinium Bromide against Candida albicans and Its Effects on Membrane Integrity.

Metal-based drugs, such as 1,10-phenanthroline, have demonstrated anticancer, antifungal and antiplasmodium activities. One of the 1,10-phenanthroline derivatives compounds (1)-N-2-methoxybenzyl-1,10-phenanthrolinium bromide (FEN), which has been demonstrated an inhibitory effect on the growth of Candida spp. This study aimed to explore the in vitro antifungal activity of FEN and its effect on the membrane integrity of Candida albicans. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of FEN against planktonic C. albicans cells were determined using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines. Cell membrane integrity was determined with the propidium iodide assay using a flow cytometer and were visualized using scanning electron microscopy (SEM). Planktonic cells growth of C. albicans were inhibited by FEN, with an MIC of 0.39-1.56 µg/mL and a MFC that ranged from 3.125 to 100 µg/mL. When C. albicans was exposed to FEN, the uptake of propidium iodide was increased, which indicated that membrane disruption is the probable mode of action of this compound. There was cells surface changes of C. albicans when observed under SEM.

Additive in vitro antiplasmodial effect of N-alkyl and N-benzyl-1,10-phenanthroline derivatives and cysteine protease inhibitor e64.

Potential new targets for antimalarial chemotherapy include parasite proteases, which are required for several cellular functions during the Plasmodium falciparum life cycle. Four new derivatives of N-alkyl and N-benzyl-1,10-phenanthroline have been synthesized. Those are (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride, and (1)-N-benzyl-1,10-phenanthrolinium iodide. Those compounds had potential antiplasmodial activity with IC(50) values from 260.42 to 465.38 nM. Cysteine proteinase inhibitor E64 was used to investigate the mechanism of action of N-alkyl and N-benzyl-1,10-phenanthroline derivatives. A modified fixed-ratio isobologram method was used to study the in vitro interactions between the new compounds with either E64 or chloroquine. The interaction between N-alkyl and N-benzyl-1,10-phenanthroline derivatives and E64 was additive as well as their interactions with chloroquine were also additive. Antimalarial mechanism of chloroquine is mainly on the inhibition of hemozoin formation. As the interaction of chloroquine and E64 was additive, the results indicated that these new compounds had a mechanism of action by inhibiting Plasmodium proteases.