Synthesis and Antifungal Activity Evaluation of Phloeodictine Analogues.

The phloeodictine-based 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-]pyrimidinium structural moiety with an -tetradecyl side chain at C-6 has been demonstrated to be a new antifungal template. Thirty-four new synthetic analogues with modifications of the bicyclic tetrahydropyrrolopyrimidinium skeleton and the N-1 side chain have been prepared and evaluated for in vitro antifungal activities against the clinically important fungal pathogens including ATCC 90113, ATCC 90028, ATCC 90030, ATCC 6258, and ATCC 90906. Nineteen compounds (, -, -, , and ) showed antifungal activities against the aforementioned five fungal pathogens with minimum inhibitory concentrations (MICs) in the range 0.

Antimicrobial Constituents from Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant , Vancomycin-Resistant , and Permeabilized Gram-Negative Pathogens.

Two new epimeric bibenzylated monoterpenes machaerifurogerol () and 5--machaerifurogerol (), and four known isoflavonoids (+)-vestitol (), 7--methylvestitol (), (+)-medicarpin (), and 3,8-dihydroxy-9-methoxypterocarpan () were isolated from Pers. This plant was previously assigned as Spruce, from which machaeriols A-D (-) and machaeridiols A-C (-) were reported, and all were then re-isolated, except the minor compound , for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data.

Identification of Antifungal Bisphosphocholines from Medicinal Species.

species including , , and are used in traditional Chinese medicine as "Qinjiao" for the treatment of rheumatism, hepatitis, and pain. Four antifungal bisphosphocholines [irlbacholine () and three new analogues, gentianalines A-C (, , and )] were identified from by a bioassay-guided fractionation and structure elucidation approach. Subsequent chemical analysis of 56 "Qinjiao" samples (45 from , five from , three from , and three from ) showed that bisphosphocholines were present in all four species, with irlbacholine as the major compound ranging from 2.

Salvia ceratophylla L. from South of Jordan: new insights on chemical composition and biological activities.

In Jordan, Salvia ceratophylla L. is traditionally used in the treatment of cancer, microbial infections, and urinary disorders. This study aimed: (1) to chemically characterize S.

Cerebrospinal Fluid and Plasma Biomarkers do not Differ in the Presenile and Late-Onset Behavioral Variants of Frontotemporal Dementia.

Background: Memory troubles and hippocampal atrophy are considered more frequent and focal atrophy less severe in late-onset (>65 years) than in presenile behavioral variant of frontotemporal dementia (bvFTD).

Objective: To compare cerebrospinal fluid (CSF) and plasma biomarkers in late-onset and presenile bvFTD.

Methods: Multicentric retrospective study (2007-2017) on patients with clinical diagnosis of bvFTD.

Synthesis and Biological Evaluation of 8-Quinolinamines and Their Amino Acid Conjugates as Broad-Spectrum Anti-infectives.

In the search of therapeutic agents for emerging drug-resistant parasites, the synthesis of newer classes of 8-quinolinamines has emerged as a successful chemotherapeutic approach. We report synthesis of 8-quinolinamines bearing 5-alkoxy, 4-methyl, and 2--butyl groups in the quinoline framework and their amino acid conjugates as broad-spectrum anti-infectives. 8-Quinolinamines exhibited potent in vitro antimalarial activity [IC = 20-4760 ng/mL (drug-sensitive D6 strain) and IC = 22-4760 ng/mL (drug-resistant W2 strain)].

Chloramphenicol Derivatives with Antibacterial Activity Identified by Functional Metagenomics.

A functional metagenomic approach identified novel and diverse soil-derived DNAs encoding inhibitors to methicillin-resistant Staphylococcus aureus (MRSA). A metagenomic DNA soil library containing 19 200 recombinant Escherichia coli BAC clones with 100 Kb average insert size was screened for antibiotic activity. Twenty-seven clones inhibited MRSA, seven of which were found by LC-MS to possess modified chloramphenicol ( Cm) derivatives, including three new compounds whose structures were established as 1-acetyl-3-propanoylchloramphenicol, 1-acetyl-3-butanoylchloramphenicol, and 3-butanoyl-1-propanoylchloramphenicol.

ANTIFUNGAL ACTIVITY OF THE ROOT EXTRACTS OF PULSATILLA PATENS AGAINST CANDIDA GLABRATA.

Plants from the genus of Pulsatilla produce a variety of secondary metabolites with biological activity. These species play a special role in herbal medicine and are used in traditional folk medicine to treat many diseases and ailments. Due to their numerous medicinal properties, they are now also widely used as homeopathic preparations.

Synthesis and Antimicrobial Evaluation of Fire Ant Venom Alkaloid Based 2-Methyl-6-alkyl-Δ-piperideines.

The first synthesis of 2-methyl-6-pentadecyl-Δ-piperideine (1), a major alkaloid of the piperideine chemotype in fire ant venoms, and its analogues, 2-methyl-6-tetradecyl-Δ-piperideine (2) and 2-methyl-6-hexadecyl-Δ-piperideine (3), was achieved by a facile synthetic method starting with glutaric acid (4) and urea (5). Compound 1 showed in vitro antifungal activity against Cryptococcus neoformans and Candida albicans with IC values of 6.6 and 12.

Antimycobacterial and antimalarial activities of endophytic fungi associated with the ancient and narrowly endemic neotropical plant Vellozia gigantea from Brazil.

Background: Endophytic fungi, present mainly in the Ascomycota and Basidiomycota phyla, are associated with different plants and represent important producers of bioactive natural products. Brazil has a rich biodiversity of plant species, including those reported as being endemic. Among the endemic Brazilian plant species, Vellozia gigantea (Velloziaceae) is threatened by extinction and is a promising target to recover endophytic fungi.

Protocol for Identifying Natural Agents That Selectively Affect Adhesion, Thickness, Architecture, Cellular Phenotypes, Extracellular Matrix, and Human White Blood Cell Impenetrability of Candida albicans Biofilms.

In the screening of natural plant extracts for antifungal activity, assessment of their effects on the growth of cells in suspension or in the wells of microtiter plates is expedient. However, microorganisms, including , grow in nature as biofilms, which are organized cellular communities with a complex architecture capable of conditioning their microenvironment, communicating, and excluding low- and high-molecular-weight molecules and white blood cells. Here, a confocal laser scanning microscopy (CLSM) protocol for testing the effects of large numbers of agents on biofilm development is described.

Two plant-derived aporphinoid alkaloids exert their antifungal activity by disrupting mitochondrial iron-sulfur cluster biosynthesis.

Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens and However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis. Several lines of evidence supported this conclusion.

Examining transgender health through the International Classification of Functioning, Disability, and Health's (ICF) Contextual Factors.

Purpose: For many transgender individuals, medical intervention is necessary to live as their desired gender. However, little is known about Contextual Factors (i.e.

Discovery of a Membrane-Active, Ring-Modified Histidine Containing Ultrashort Amphiphilic Peptide That Exhibits Potent Inhibition of Cryptococcus neoformans.

The new structural classes of ultrashort peptides that exhibit potent microbicidal action have potential as future drugs. Herein, we report that C-2 arylated histidines containing tripeptides His(2-Ar)-Trp-His(2-Ar) exhibit potent antifungal activity against Cryptococcus neoformans with high selectivity. The most potent peptide 12f [His(2-biphenyl)-Trp-His(2-biphenyl)] displayed high in vitro activity against C.

Synthesis, stability and mechanistic studies of potent anticryptococcal hexapeptides.

The growing incidents of cryptococcosis in immuno-compromised patients have created a need for novel drug therapies capable of eradicating the disease. The peptide-based drug therapy offers many advantages over the traditional therapeutic agents, which has been exploited in the present study by synthesizing a series of hexapeptides that exhibits promising activity against a panel of Gram-negative and Gram-positive bacteria and various pathogenic fungal strains; the most exemplary activity was observed against Cryptococcus neoformans. The peptides 3, 24, 32 and 36 displayed potent anticryptococcal activity (IC = 0.

Biological evaluation of phytoconstituents from Polygonum hydropiper.

Fourteen compounds including vanicoside B (1), vanicoside F (2), vanicoside E (3) and 5,6-dehydrokawain (4), aniba-dimer-A (5), 6,6'-((1α,2α,3β,4β)-2,4-diphenylcyclobutane-1,3-diyl)bis(4-methoxy-2H-pyran-2-one) (6), (+)-ketopinoresinol (7), isorhamnetin (8), 3,7-dihydroxy-5,6-dimethoxy-flavone (9), isalpinin (10), cardamomin (11), pinosylvin (12), 2-desoxy-4-epi-pulchellin (13) and β-sitosterol (14) were isolated from dichloromethane-soluble portion of Polygonum hydropiper. By using Alamar blue assay, compounds 2, 7, 8, 11 and 12 were found to be active against Trypanosoma brucei with IC values in the range of 0.49-7.

Bioactive Formylated Flavonoids from Eugenia rigida: Isolation, Synthesis, and X-ray Crystallography.

Two new flavonoids, rac-6-formyl-5,7-dihydroxyflavanone (1) and 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (2), together with five known derivatives, rac-8-formyl-5,7-dihydroxyflavanone (3), 4',6'-dihydroxy-2'-methoxy-3'-methyldihydrochalcone (4), rac-7-hydroxy-5-methoxy-6-methylflavanone (5), 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone (6), and 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7), were isolated from the leaves of Eugenia rigida. The individual (S)- and (R)-enantiomers of 1 and 3, together with the corresponding formylated flavones 8 (6-formyl-5,7-dihydroxyflavone) and 9 (8-formyl-5,7-dihydroxyflavone), as well as 2',4',6'-trihydroxychalcone (10), 3'-formyl-2',4',6'-trihydroxychalcone (11), and the corresponding 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7) and 2',4',6'-trihydroxydihydrochalcone (12), were synthesized. The structures of the isolated and synthetic compounds were established via NMR, HRESIMS, and electronic circular dichroism data.

Synthesis of Natural Acylphloroglucinol-Based Antifungal Compounds against Cryptococcus Species.

Thirty-three natural-product-based acylphloroglucinol derivatives were synthesized to identify antifungal compounds against Cryptococcus spp. that cause the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C.

Phloroglucinol and Terpenoid Derivatives from Hypericum cistifolium and H. galioides (Hypericaceae).

A new simple phloroglucinol derivative characterized as 1-(6-hydroxy-2,4-dimethoxyphenyl)-2-methyl-1-propanone (1) was isolated from Hypericum cistifolium (Hypericaceae) as a major constituent of the non-polar plant extract. Minor amounts of this new compound, in addition to two known structurally related phloroglucinol derivatives (2 and 3), and two new terpenoid derivatives characterized, respectively, as 2-benzoyl-3,3-dimethyl-4R,6S-bis-(3-methylbut-2-enyl)-cyclohexanone (4a) and 2-benzoyl-3,3-dimethyl-4S,6R-bis-(3-methylbut-2-enyl)-cyclohexanone (4b), were isolated from a related species, H. galioides Lam.

Synthesis and Biological Evaluation of 3,5-Dimethoxystilbene Analogs.

In our continuing effort to discover natural product-based pest management agents, derivatives of 3,5-dimethoxystilbene were synthesized yielding 27 new and six known compounds. Compounds 11 and 12 showed strong Aedes aegypti larvicidal activity (LC 45.31 and 49.

Antifungal Amide Alkaloids from the Aerial Parts of Piper flaviflorum and Piper sarmentosum.

Sixty-three amide alkaloids, including three new, piperflaviflorine A (), piperflaviflorine B (), and sarmentamide D (), and two previously synthesized ones, (1,3)-1-cinnamoyl-3- hydroxypyrrolidine () and -[7'-(4'-methoxyphenyl)ethyl]-2-methoxybenzamide (), were isolated from the aerial parts of and Their structures were elucidated by detailed spectroscopic analysis and, in case of , by single-crystal X-ray diffraction. Most of the isolates were tested for their antifungal and antibacterial activities. Ten amides (-) showed antifungal activity against ATCC 90 113 with IC values in the range between 4.

New ent-Clerodane and Abietane Diterpenoids from the Roots of Kenyan Croton megalocarpoides Friis & M. G. Gilbert.

The roots of the endangered medicinal plant Croton megalocarpoides collected in Kenya were investigated and twenty-two compounds isolated. Among them were twelve new ent-clerodane (1-12) and a new abietane (13) diterpenoids, alongside the known crotocorylifuran (4 a), two known abietane and four known ent-trachylobane diterpenoids, and the triterpenoids, lupeol and acetyl aleurotolic acid. The structures of the compounds were determined using NMR, HRMS and ECD.

Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads.

Background: Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT.

Diversity-oriented natural product platform identifies plant constituents targeting Plasmodium falciparum.

Background: A diverse library of pre-fractionated plant extracts, generated by an automated high-throughput system, was tested using an in vitro anti-malarial screening platform to identify known or new natural products for lead development. The platform identifies hits on the basis of in vitro growth inhibition of Plasmodium falciparum and counter-screens for cytotoxicity to human foreskin fibroblast or embryonic kidney cell lines. The physical library was supplemented by early-stage collection of analytical data for each fraction to aid rapid identification of the active components within each screening hit.