Synthesis, anticancer activity, SAR and binding mode of interaction studies of substituted pentanoic acids: part II

Aim: Our previous results suggest that phenyl/naphthylacetyl pentanoic acid derivatives may exhibit dual MMP-2 and HDAC8 inhibitory activities and show effective cytotoxic properties. Methodology: Here, 13 new compounds (C1–C13) were synthesized and characterized. Along with these new compounds, 16 previously reported phenyl/napthylacetyl pentanoic acid derivatives (C14–C29) were biologically evaluated. Results: Compounds C6 and C27 showed good cytotoxicity against leukemia cell line Jurkat E6.1. The mechanisms of cytotoxicity of these compounds were confirmed by DNA deformation assay and reactive oxygen species assay. MMP-2 and HDAC8 expression assays suggested the dual inhibiting property of these two compounds. These findings were supported by results of molecular docking studies. In silico pharmacokinetic properties showed compounds C6 and C27 have high gastrointestinal absorption. Conclusion: This study highlights the action of phenyl/naphthylacetyl pentanoic acid derivatives as anticancer agents.

Identification on chemical organic compounds of Macaranga hypoleuca by using Py-GCMS

Organic chemical compounds of Macaranga spp. have been identified and their bioactive potential have been explored, but Macaranga hypoleuca information was limited. M. hypoleuca includes fast growing and pioneer’s species in secondary forest successions. Limited utilization of M. hypoleuca make this species classified into less well-known species. Present study was conducted to identify the chemical compounds of M. hypoleuca by using Pyrolysis Gas Chromatography-Mass Spectrometry (Py-GCMS QP2010). Samples were originated from stem, bark, sap and leaves of M. hypoleuca. This study was able to identify the compounds of dibromo chloropropane, methoxy 2-propenal, ammonium carbamate, levoglucosan, teraxeron, n-tetra terakseron, hydroxy-2-propenal, carbinol and pentanoic acid as the dominant organic compounds in M. hypoleuca. Further research is needed to isolate and biological activity.

In Vitro Evaluation of the Squaramide-Conjugated Fibroblast Activation Protein Inhibitor-Based Agents AAZTA5.SA.FAPi and DOTA.SA.FAPi

Recently, the first squaramide-(SA) containing FAP inhibitor-derived radiotracers were introduced. DATA5m.SA.FAPi and DOTA.SA.FAPi with their non-radioactive complexes showed high affinity and selectivity for FAP. After a successful preclinical study with [68Ga]Ga-DOTA.SA.FAPi, the first patient studies were realized for both compounds. Here, we present a new squaramide-containing compound targeting FAP, based on the AAZTA5 chelator 1,4-bis-(carboxylmethyl)-6-[bis-(carboxymethyl)-amino-6-pentanoic-acid]-perhydro-1,4-diazepine. For this molecule (AAZTA5.SA.FAPi), complexation with radionuclides such as gallium-68, scandium-44, and lutetium-177 was investigated, and the in vitro properties of the complexes were characterized and compared with those of DOTA.SA.FAPi. AAZTA5.SA.FAPi and its derivatives labelled with non-radioactive isotopes demonstrated similar excellent inhibitory potencies compared to the previously published SA.FAPi ligands, i.e., sub-nanomolar IC50 values for FAP and high selectivity indices over the serine proteases PREP and DPPs. Labeling with all three radiometals was easier and faster with AAZTA5.SA.FAPi compared to the corresponding DOTA analogue at ambient temperature. Especially, scandium-44 labeling with the AAZTA derivative resulted in higher specific activities. Both DOTA.SA.FAPi and AAZTA5.SA.FAPi showed sufficiently high stability in different media. Therefore, these FAP inhibitor agents could be promising for theranostic approaches targeting FAP.

Biocatalytic Conversion of Short-Chain Fatty Acids to Corresponding Alcohols in Escherichia coli

Advanced biofuels possess superior characteristics to serve for gasoline substitutes. In this study, a whole cell biocatalysis system was employed for production of short-chain alcohols from corresponding fatty acids. To do so, Escherichia coli strain was equipped with a biocatalytic pathway consisting of endogenous atoDA and Clostridium acetobutylicum adhE2. The strain was further reprogrammed to improve its biocatalytic activity by direction the glycolytic flux to acetyl-CoA and recycling acetate. The production of 1-propanol and n-pentanol were exemplified with the engineered strain. By substrate (glucose and propionate) feeding, the strain enabled production of 5.4 g/L 1-propanol with productivity reaching 0.15 g/L/h. In addition, the strain with a heavy inoculum was implemented for the n-pentanol production from n-pentanoic acid. The production titer and productivity finally attained 4.3 g/L and 0.86 g/L/h, respectively. Overall, the result indicates that this developed system is useful and effective for biocatalytic production of short-chain alcohols.

Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents

2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6H-pyran[a]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism Stachybotrys longispora FG216, which showed moderate antithrombotic(fibrinolytic) activity. To further enhance its antithrombotic effect, a series of new FGFC1 derivatives (F1–F7) were synthesized via chemical modification at C-2 and C-2′ phenol groups moieties and C-1″ carboxyl group. Their fibrinolytic activities in vitro were evaluated. Among the derivatives, F1–F4 and F6 showed significant fibrinolytic activities with EC50 of 59.7, 87.1, 66.6, 82.8, and 42.3 μM, respectively, via enhancement of urokinase activity. Notably, derivative F6 presented the most remarkable fibrinolytic activity (2.72-fold than that of FGFC1). Furthermore, the cytotoxicity of derivative F6 was tested as well as expression of Fas/Apo-1 and IL-1 on HeLa cells. The results showed that, compared to FGFC1, derivative F6 possessed moderate cytotoxicity and apoptotic effect on HeLa cells (statistical significance p > 0.1), making F6 a potential antithrombotic agent towards clinical application.

Odorous Compound Removal Performance and Water Properties of a Biotrickling Filter Installed in a Piggery

Highlights We evaluated the performance of a two-stage biotrickling filter in a pig facility. A short empty bed residence time lowered the secondary filter removal efficiency for many odorous compounds. The removal efficiency of some compounds increased when the pH in the secondary water tank decreased. Low-odor-threshold compounds such as MT, n-BA, n-PA, and p-cresol were indicated as targets for optimization. Abstract . Odor is a major problem in pig production, and it is important to minimize odor emissions. To determine the factors influencing variations in odor removal efficiency, we analyzed the performance of a biotrickling filter installed in growing-finishing pig rooms on a commercial farm. Over 16 months, we conducted measurements of representative odorous compounds, namely sulfur compounds (hydrogen sulfide, methanethiol, dimethyl sulfide, and dimethyl disulfide), volatile fatty acids (propanoic acid, 2-methylpropanoic acid, butanoic acid, 3-methylbutanoic acid, and pentanoic acid), and ammonia. The average removal efficiencies of methanethiol, dimethyl disulfide, volatile fatty acids, and ammonia were 83% to 89%, with 50% for hydrogen sulfide and 18% for dimethyl sulfide. For many, but not all, odorous compounds, removal efficiency declined significantly with decreasing empty bed residence time (EBRT). From an analysis of the correlations of odorous compounds’ removal efficiency with the properties of the trickling water, we hypothesized that water properties such as pH, free ammonia, free nitrous acid, ionic species (Na+, Ca2+) concentrations, temperature, electrical conductivity, and biological oxygen demand, in addition to EBRT, were associated with fluctuations in removal efficiency during full-scale operation. The pH in the secondary water tank was negatively correlated with the removal efficiencies of methanethiol, dimethyl sulfide, butanoic acid, 3-methylbutanoic acid, pentanoic acid, and ammonia. Our identification of key odorous compounds indicates the importance of the secondary filter in odor treatment. Biotrickling filters for air in pig facilities could be further optimized by targeting low-odor-threshold compounds such as methanethiol, butanoic acid, pentanoic acid, and p-cresol, in addition to ammonia. Keywords: Ammonia, Biotrickling filter, Pig facility odor, Sulfur compound, Trickling water, Volatile fatty acid.

Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry

Gas chromatography-ion mobility spectrum (GC-IMS) is used to analyze and compare the differences in aroma among different tobacco samples. The aroma substances in tobacco samples in Jilin Changchun are the richest, while those in Guangdong Nanxiong are the lowest. The concentrations of aroma substances such as decanal, 1-hydroxy-2-propanone, and 2-methylbutanol were the highest in Guangdong Nanxiong of the three. The concentration of 1-hexanol, cyclohexanone, pentanoic acid, and other aroma substances in Fujian Nanping was high. The concentration of 2-acetylfuran, 2-octanol, isopentanol, 3-methylvaleric acid, phenylacetic acid, and other aroma substances in Changchun area of Jilin Province was low. Through principal component analysis and similarity research, both tobaccos can be distinguished by their production areas and grades from the same.

Natural Products from Octocorals of the Genus Dendronephthya (Family Nephtheidae)

In this review, 170 natural substances, including steroid, diterpenoid, sesquiterpenoid, peptide, prostaglandin, base, chlorolipid, bicyclolactone, amide, piperazine, polyketide, glycerol, benzoic acid, glycyrrhetyl amino acid, hexitol, pentanoic acid, aminoethyl ester, octadecanone, alkaloid, and a 53-kD allergenic component from octocorals belonging to genus Dendronephthya, were listed. Some of these compounds displayed potential bioactivities.