Recent advances on synthesis and biological activities of aurones.

Aurones are naturally occurring structural isomerides of flavones that have diverse bioactivities including antiviral, antibacterial, antifungal, anti-inflammatory, antitumor, antimalarial, antioxidant, neuropharmacological activities and so on. They constitute an important class of pharmacologically active scaffolds that exhibit multiple biological activities via diverse mechanisms. This review article provides an update on the recent advances (2013-2020.4) in the synthesis and biological activities of these derivatives. In the cases where sufficient information is available, some important structure-activity relationships (SAR) of their biological activities were presented, and on the strength of our expertise in medicinal chemistry and careful analysis of the recent literature, for the potential of aurones as medicinal drugs is proposed.

Template synthesis, spectroscopic studies, antimicrobial, nematicidal and pesticidal activities of chromium(III) macrocyclic complexes.

A new series of Cr(III) macrocyclic complexes have been synthesized by template condensation of ligands 2-[4-chloro-2-(2-oxo-1,2-diphenyl-ethylideneamino)-phenylimino]-1,2-diphenyl-ethanone (ML(1)) and 2-[4-fluro-2-(2-oxo-1,2-diphenyl-ethylideneamino)-phenylimino]-1,2-diphenyl-ethanone (ML(2)) respectively, with appropriate diamines i.e. 1,2-phenylenediamine, 4- chloro 1,2-phenylenediamine and 4-fluro- 1,2-phenylenediamine in the presence of CrCl(3).6H(2)O. The ligands and their complexes have been characterized on the basis of elemental analyses, molecular weight determinations, conductance and magnetic susceptibility measurements and spectral studies including IR, ESR, electronic spectra and X-ray powder diffraction studies. On the basis of these studies, a six-coordinated octahedral geometry has been proposed for all these complexes. The newly synthesized ligands and their complexes have been screened for their antimicrobial, nematicidal and pesticidal activities. The results are indeed positive.

Identification and characterization of a dual-acting antinematodal agent against the pinewood nematode, Bursaphelenchus xylophilus.

The pinewood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of the pine wilt disease, which has become a major threat to pine forests throughout the world. Despite the availability of several preventive trunk-injection agents, no therapeutic trunk-injection agent for eradication of PWN currently exists. In the characterization of basic physiological properties of B. xylophilus YB-1 isolates, we established a high-throughput screening (HTS) method that identifies potential hits within approximately 7 h. Using this HTS method, we screened 206 compounds with known activities, mostly antifungal, for antinematodal activities and identified HWY-4213 (1-n-undecyl-2-[2-fluorphenyl] methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a highly water-soluble protoberberine derivative, as a potent nematicidal and antifungal agent. When tested on 4 year-old pinewood seedlings that were infected with YB-1 isolates, HWY-4213 exhibited a potent therapeutic nematicidal activity. Further tests of screening 39 Caenorhabditis elegans mutants deficient in channel proteins and B. xylophilus sensitivity to Ca(2+) channel blockers suggested that HWY-4213 targets the calcium channel proteins. Our study marks a technical breakthrough by developing a novel HTS method that leads to the discovery HWY-4213 as a dual-acting antinematodal and antifungal compound.

Design, synthesis, and biological evaluation of a library of 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides.

A library of 422 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxamides was prepared in five steps using solution-phase chemistry. The first step in the synthesis was the reaction of ethyl 2-ethoxymethylene-3-oxo-4,4,4-trifluorobutanoate with thiosemicarbazide, which is reported in the literature to afford a 1:1 mixture of ethyl 1-thiocarbamoyl-5-(trifluoromethyl)pyrazole-4-carboxylate and ethyl 1-thiocarbamoyl-3-(trifluoromethyl)pyrazole-4-carboxylate. We reassigned the structure of the product to be a single compound, ethyl 5-hydroxy-1-thiocarbamoyl-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-4-carboxylate. This common intermediate was diversified by reaction with 17 alpha-bromoketones affording, in two steps, 17 1-(2-thiazolyl)-5-(trifluoromethyl)pyrazole-4-carboxylic acids. Scavenger resins were used to facilitate formation and purification of up to 27 amides from each of these acids in the last step. In addition, the Curtius reaction was applied to 12 of the acids followed by quenching with alcohols to afford a 108-member carbamate library. Certain compounds in the two libraries were toxic to C. elegans.

Pesticidal properties of parthenin (from Parthenium hysterophorus) and related compounds.

Eleven sesquiterpene lactone derivatives of parthenin (1), obtained from wild feverfew, Parthenium hysterophorus, were prepared by chemical and photochemical transformations. The compounds tested were a pyrazoline adduct (2) of parthenin, its cyclopropyl (3) and propenyl (4) derivatives, anhydroparthenin (5), a dihydro-deoxygenated product (6), a formate (7) and its corresponding alcohol (8) and acetate (9), a rearranged product (10), lactone (11) and hemiacetal (12). All these derivatives, along with parthenin, were tried for their antifeedant action against sixth-instar larvae of Spodoptera litura, for insecticidal activity against the adults of store grain pest Callosobruchus maculatus, for phytotoxic activity against Cassia tora, and for nematicidal activity against the juvenile stage-II (J2) of the root knot nematode Meloidogyne incognita. Antifeedent bioassay revealed that parthenin is moderately antifeedant. Among the derivatives, the saturated lactone (11) was found to be about 2.25 times more active than parthenin. The pyrazoline adduct (2) was found to be the most effective as an insecticide, with LC50 values after 24, 48 and 72 h of 96, 43 and 32 mg litre-1, respectively, which are comparable with neem extract. Compound 4 was found to be the most effective inhibitor of germination and seedling growth of C tora, with ID50 values for germination, plumule length and radicle length of 136, 326 and 172 compared with 364, 738 and 427 mg litre-1, respectively, for parthenin. Compound 10 was found to be the most effective in terms of nematicidal activity. The LC50 values for this compound were 273 and 104 mg litre-1, respectively, after 48 and 72 h compared with 862 and 512 mg litre-1 observed for parthenin after 48 and 72 h.

[The synthesis and study of the trichinellacidal activity of bromine and chlorine derivatives of 8-quinolyloxysalicylanilides]. / Sintez i izuchenie trikhinellotsidnoi aktivnosti nekotorykh brom- i khlorproizvodnykh 8-khinoliloksisalitsilanilidov.

Some new bromine (chlorine) derivatives of 8-quinolyloxysalicylanilides were synthesized and tested for trichinellacidal activity. Among them there was the substance N-[3-bromophenyl-4-(5-chloroquinolinoxy)]-3,5-dibromosalicylami de which exhibited its high trichinellocidal activity (in albino mice infected with decapsulated Trichinella spiralis) that was close to that of mebendazole.

Synthesis and nematocidal activity of diarylnonanoids related to malabaricones.

Twenty diarylnonanones were synthesized and their nematocidal activity was examined. Among those, the p-hydroxy compound 16 exhibited the strongest activity comparable to the natural diarylnonanoids, malabaricones A and C. Diarylundecanoid 57 also showed appreciable activity.

[The technology for manufacturing antiparasitic preparations. 7. Preparation G-1460 and its use for the treatment of monieziasis and intestinal nematodiases]. / Tekhnologiia proizvodstva protivoparazitarnykh preparatov. 7. Preparat G-1460 i ego primenenie dlia lecheniia moniezioza i kishechnykh nematodozov.

A procedure was developed for the synthesis of the anthelminthic G-1460. The therapeutical doses (20 and 25 mg/kg) of the agent were defined for the treatment of monieziasis and gastrointestinal nematodes on an individual basis.

[The synthesis and study of the acute toxicity and anthelmintic activity of new 2-methylthiobenzimidazoles]. / Sintez, izuchenie ostroi toksichnosti i protivogel'mintnoi aktivnosti novykh 2-metiltiobenzimidazolov.

Several derivatives of 2-methylthiobenzimidazoles were synthesized and assayed for anthelmintic activity. Following these studies, 2-methylthio-5-(1-chloronaphthyloxy-2)-6-chlorobenzimidazole (G-1557) has been selected as a tichinellacide for detailed investigations.

[The technology for manufacturing antiparasitic preparations. 3. The development of a technology for producing the anthelmintic embovin (pyrantel embonate) in finely dispersed form and the evaluation of its anthelmintic properties]. / Tekhnologiia proizvodstva protivoparazitarnykh preparatov. 3. Razrabotka tekhnologii polucheniia antigel'mintika émbovina (pirantelia émbonata) v melkodispersnoi forme i otsenka ego protivogel'mintnykh svoistv.

Manufacturing process for anthelmintic embovin in a micronized form have been developed. Embovin in the micronized form exhibited the highest activity.

[The synthesis and study of the acute toxicity and anthelmintic activity of salicylanilides containing a quinoline residue]. / Sintez, izuchenie ostroi toksichnosti i protivogel'mintnoi aktivnosti salitsilanilinov, soderzhashchikh ostatok khinolina.

Salicylanilides containing quinoline moiety were synthesized and examined for acute toxicity and antinematodal activity. All the compounds were shown to possess a low toxicity. In the trials on a nematodal model (Aspiculuris tetraptera, white mice), 2 compounds--G-1570 and G-1575--were shown to be highly effective.