Synthesis,characterization and antimicrobial activities of triorganotin(IV) complexes with azo-azomethine carboxylate ligands: crystal structure of a tributyltin(IV) and a trimethyltin(IV) complex

Triorganotin(IV) complexes with polyaromatic azo-azomethine carboxylate ligands viz. 2-{4-hydroxy-3-[(2/4-hydroxyphenylimino)methyl]phenylazo}benzoic acids [H₃L¹/H₃L²] were synthesized by reacting the ligands with either bis-tri-n-butyltin(IV) oxide (for 1 and 4) or trimethyltin(IV) chloride in presence of triethylamine (for 2 and 5) or triphenyltin(IV) hydroxide (for 3 and 6). The complexes were characterized by elemental analysis, UV, IR, NMR, and mass spectrometry. NMR spectroscopic studies of the compounds suggested that the complexes adopt four-coordinate tetrahedral geometry around tin in solution. Molecular structures of 1 and 2 were determined by single-crystal X-ray diffraction. Both complexes have distorted trigonal bipyramidal geometry around tin in the solid state. Compound 1 is a one-dimensional (1-D) double chain coordination polymer which can be described as two different 24- and 30-membered non-porous macrocyclic rings constructed from two tributyltin units and two ligand moieties. The structure of 2 comprises a discrete cyclic centrosymmetric dimer with two lattice water molecules per formula unit. In the dimer, two trimethyltin entities are bridged by two ligand moieties. The dimers are further interconnected with lattice water molecules by multiple O–H?O hydrogen bonds to form a 1-D H-bonded network. The complexes were also screened for their antimicrobial activities.     

Effect of processing on the release of phenolic compounds and antioxidant activity during in vitro digestion of hulless barley

Hulless barley contains phenolic compounds and possesses various antioxidant activities. To clarify the effects of thermal processing and in vitro digestion on the release of phenolic compounds in hulless barley, we studied the phenolic components and antioxidant activities of hulless barley after steaming, roasting processes, and in vitro digestions. Both total phenolic content (TPC) and total flavonoid content (TFC) in raw hulless barley (HB, 4.14 mg/g DW and 1.53 mg/g DW, respectively) were higher than that of steamed hulless barley (SHB) and roasted hulless barley (RHB). In vitro digestion significantly released more ferulic acid from its bound form, but hydrolyzed some amount of flavonoid (luteolin). Chrysoeriol-7-O-glucouronide was significantly detected (412.13 µg/g DW in HB, 382.19 µg/g DW in SHB, and 396.91 µg/g DW in RHB) in all three hulless barley. The total released content of phenolic compounds obtained from each phase after digestion reached to 46% and 45% for SHB and RHB, which was higher than that in the HB (41%). The antioxidant assay (via DPPH and ABTS free radical scavenging assays) indicated that the capacity of HB was obviously higher than that of SHB and RHB in undigested group. For digested group, the ABTS⁺ assay order was following, undigested > oral > small intestine > gastric > large intestine. The DPPH assay results indicated the antioxidant capacity as the order of undigested > oral > gastric > large intestine. Correlation analysis showed that ferulic acid, chrysoeriol-7-O-glucouronide, luteolin, chrysoeriol, and luteolin-7-O-glucouronide contributed to the antioxidant activities. Hierarchical cluster analysis (HCA) grouped samples accordingly. Roasting process could be considered as a better daily thermal treatment for hulless barley than steaming in terms of phenolic compounds and their antioxidant activities.     

Insights into the synthesis and mechanism of green synthesized antimicrobial nanoparticles,answer to the multidrug resistance

Emergence of the multidrug resistant human pathogenic strains is posing a serious health challenge. Resistant strains carry mutations which help them to resist conventional drugs. Therefore, it is required to produce more effective agents that are able to degrade the resistant pathogenic bacterial strains. The antimicrobial properties of nanoparticles (NPs) by eco-friendly green synthetic methods have pulled attention everywhere owing to their exceptional properties and small particle size of 100 nm. NPs are considered to belong to a group of antimicrobial agents which have ability to go inside microbial cells and kill them. In this comprehensive review, we are discussing the green synthetic methods used for the synthesis of NPs targeting the microbes. Additionally, several characterization techniques of antimicrobial NPs are also discussed. Subsequently, various methods used for the analysis of antimicrobial activities and their mechanisms are also examined.     

Highly Aromatic Flavan-3-ol Derivatives from Palaeotropical Artocarpus lacucha Buch.-Ham Possess Radical Scavenging and Antiproliferative Properties

Phytochemical investigation of leaves and stembark of Artocarpus lacucha collected in Thailand resulted in three yet undescribed isomeric flavan-3-ol derivatives (1–3), the four known compounds gambircatechol (4), (+)-catechin (5), (+)-afzelechin (6) and the stilbene oxyresveratrol (7). Compounds 1 to 3 feature 6/6/5/6/5/6 core structures. All structures were deduced by NMR and MS, while density functional theory (DFT) calculations on B3LYP theory level were performed of compounds 1 to 3 to support the stereochemistry in positions 2 and 3 in the C-ring. Possible biosynthetic pathways leading to 4 are discussed. The DPPH assay revealed high radical scavenging activities for 1 (EC₅₀ = 9.4 ± 1.0 µmol mL⁻¹), 2 (12.2 ± 1.1), 3 (10.0 ± 1.5) and 4 (19.0 ± 2.6), remarkably lower than ascorbic acid (EC₅₀ = 34.9) and α-tocopherol (EC₅₀ = 48.6). A cytotoxicity assay revealed moderate but consistent antiproliferative properties of 1 in CH1/PA-1 (ovarian teratocarcinoma) and SW480 (colon carcinoma) cells, with IC₅₀ values of 25 ± 6 and 34 ± 4 µM, respectively, whereas effects in A549 (non-small cell lung cancer) cells were rather negligible. The performed DCFH-DA assay of 1 in the former cell lines confirmed potent antioxidative effects even in the cellular environment.     

Chemical Composition,Antioxidant and Cytoprotective Potentials of Carica papaya Leaf Extracts: A Comparison of Supercritical Fluid and Conventional Extraction Methods

The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO₂) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H₂O₂) assay. Both C. papaya leaf scCO₂ extract with 5% ethanol (CPSCE) and C. papaya leaf scCO₂ extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H₂O₂-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H₂O₂. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.     

Secondary Metabolites of the Genus Amycolatopsis: Structures,Bioactivities and Biosynthesis

Actinomycetes are regarded as important sources for the generation of various bioactive secondary metabolites with rich chemical and bioactive diversities. Amycolatopsis falls under the rare actinomycete genus with the potential to produce antibiotics. In this review, all literatures were searched in the Web of Science, Google Scholar and PubMed up to March 2021. The keywords used in the search strategy were “Amycolatopsis”, “secondary metabolite”, “new or novel compound”, “bioactivity”, “biosynthetic pathway” and “derivatives”. The objective in this review is to summarize the chemical structures and biological activities of secondary metabolites from the genus Amycolatopsis. A total of 159 compounds derived from 8 known and 18 unidentified species are summarized in this paper. These secondary metabolites are mainly categorized into polyphenols, linear polyketides, macrolides, macrolactams, thiazolyl peptides, cyclic peptides, glycopeptides, amide and amino derivatives, glycoside derivatives, enediyne derivatives and sesquiterpenes. Meanwhile, they mainly showed unique antimicrobial, anti-cancer, antioxidant, anti-hyperglycemic, and enzyme inhibition activities. In addition, the biosynthetic pathways of several potent bioactive compounds and derivatives are included and the prospect of the chemical substances obtained from Amycolatopsis is also discussed to provide ideas for their implementation in the field of therapeutics and drug discovery.     

Genomic and Metabolomic Investigation of a Rhizosphere Isolate Streptomyces netropsis WLXQSS-4 Associated with a Traditional Chinese Medicine

Rhizosphere microorganisms play important ecological roles in promoting herb growth and producing abundant secondary metabolites. Studies on the rhizosphere microbes of traditional Chinese medicines (TCMs) are limited, especially on the genomic and metabolic levels. In this study, we reported the isolation and characterization of a Steptomyces netropsis WLXQSS-4 strain from the rhizospheric soil of Clematis manshurica Rupr. Genomic sequencing revealed an impressive total of 40 predicted biosynthetic gene clusters (BGCs), whereas metabolomic profiling revealed 13 secondary metabolites under current laboratory conditions. Particularly, medium screening activated the production of alloaureothin, whereas brominated and chlorinated pimprinine derivatives were identified through precursor-directed feeding. Moreover, antiproliferative activities against Hela and A549 cancer cell lines were observed for five compounds, of which two also elicited potent growth inhibition in Enterococcus faecalis and Staphylococcus aureus, respectively. Our results demonstrated the robust secondary metabolism of S. netropsis WLXQSS-4, which may serve as a biocontrol agent upon further investigation.     

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design,Synthesis, Biological,Molecular Docking Studies and In Silico ADME Evaluation

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC₅₀ = 11 ± 1 µM) with an IC₅₀ value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.     

NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.     

Densazalin,a New Cytotoxic Diazatricyclic Alkaloid from the Marine Sponge Haliclona densaspicula

Densazalin, a polycyclic alkaloid, was isolated from the marine sponge Haliclona densaspicula collected in Korea. The complete structure of the compound was determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, high-resolution mass spectrometry, and comparison of the calculated and measured electronic circular dichroism spectra. Densazalin possesses a unique 5,11-diazatricyclo[7.3.1.0^2,7]tridecan-2,4,6-triene moiety, which is connected by two linear carbon chains. This compound was derived from the biogenetic precursor bis-1,3-dialkylpyridnium. Densazalin exhibited cytotoxic activity on two human tumor cell lines (AGS and HepG2) in the Cell Counting Kit-8 (CCK-8) bioassay, with IC₅₀ values ranging from 15.5 to 18.4 μM.