New 2,6-dinitroaniline derivatives with an antimitotic effect and their synergistic activity in the compositions with graminicides

Antimitotic activity of new dinitroaniline derivatives was determined, and their ability to induce apoptosis in plant cells in compositions with inhibitors of acetyl-CoA carboxylase was studied.     

Antimitotic activity of new 2,6-dinitroaniline derivatives and their synergistic activity in compositions with graminicides

Shown antimicrotrubules activity of new 2,6-dinitroaniline compounds. Investigated their ability on apoptotic processes in a plant cell when used as a composition with inhibitors of acetyl-CoA carboxylase.     

Synthesis and antidiabetic activity of some new chromonyl-2,4-thiazolidinediones

A series of chromonyl-2,4-thiazolidinediones/imidazolidinediones/2-thioxo-imidazolidine-4-ones (IIIa–i, IVa–i) was prepared by Knoevenagel reaction of 2,4-thiazolidinedione/2,4-imidazolidinedione/2-thioxo-imidazolidine-4-one (IIa–c) with 2/3-formyl chromone (Ia–b) and then alkylation with methyl/ethyl iodide. The prepared compounds were tested for their insulinotropic activities in INS-1 cells. Compounds ?Vb and ?Vc (at lower concentration, 1?μg/mL) were able to increase insulin release in the presence of 5.6?mmol/L glucose.” should be written as “Compounds IVb and IVc (at lower concentration, 1?µg/mL) and also IIId and IIIg (at higher concentration) were able to increase insulin release in the presence of 5.6?mmol/L glucose. Compounds ?Vb and ?Vc (at lower concentration, 1?μg/mL) were able to increase insulin release in the presence of 5.6?mmol/L glucose.     

Synthesis and biological activity of some new flavonyl-2,4-thiazolidinediones

A new series of flavonyl-2,4-thiazolidinediones (Va-c, VIa-c) was prepared by Knoevenagel reaction. The synthesized compounds were tested for their ability to inhibit rat kidney aldose reductase (AR) and for their insulinotropic activities in INS-1 cells. Compound Vb was able to increase insulin release in the presence of 5.6mmol/l glucose. Compounds VIa-c displayed moderate to high AR inhibitory activity levels. Particularly, compound VIa showed the highest AR inhibitory activity (86.57%).     

Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs

The syntheses and antimitotic activity of several novel 2-methoxyestradiol analogs are described. Structural modifications investigated include introduction of additional unsaturation in rings B and D; inversion at C-13; and substitution at the C-2, C-15, C-16, and C-7 alpha positions. Of 15 analogs synthesized, 2 have demonstrated superior biological activities compared to 2-methoxyestradiol.     

Genotoxicity of 2,4- and 2,6-dinitrotoluene as measured by the Tradescantia micronucleus (Trad-MCN) bioassay

The phytogenotoxicity of 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) was assessed using the Tradescantia micronucleus (Trad-MCN) bioassay. Tradescantia cuttings bearing young inflorescences were exposed for 6h to 2,4- or 2,6-DNT amended water solutions up to their respective solubilities. The nominal concentrations were 0, 1.9, 3.8, 7.5, 15, 30, 60, 100, 150, 200mg/l of 2,4-DNT, and 0, 7.5, 15, 30, 60, 90, 120, 180mg/l of 2,6-DNT. Each treatment was repeated three or four times. Chemical concentrations in test solutions were analyzed prior to and after the exposure. Cadmium chloride (0-20mM) was used as the positive control. Micronuclei (MCN) were scored in the tetrad-stage pollen mother cells. The MCN frequency (%), i.e. the number of micronuclei scored in 100 tetrads, was the measurement endpoint. Results indicated that both 2,4-DNT and 2,6-DNT were genotoxic with the minimum effective dose (MED) of 30 and 135mg/l, respectively. Longer exposure (30h) without recovery time at 150mg/l of 2,4-DNT and 180mg/l of 2,6-DNT did not induce significantly higher MCN frequencies.     

Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs--Part II

The syntheses and antimitotic activity of several novel 18a-homo-analogs of 2-methoxyestradiol are described. Structural modifications of the parent 2-methoxy-18a-homoestradiol include introduction of unsaturation in the D-ring and methylation of the 17-OH. Of seven analogs synthesized, one has demonstrated superior biological activities compared to 2-methoxyestradiol. The relationship between biological activity and the conformational preference of the 13-ethyl group as determined by computational analysis is discussed.     

Synthesis and antimicrobial activity of some new thiazolyl thiazolidine-2,4-dione derivatives

In this study, a series of thiazolyl thiazolidine-2,4-dione derivatives (Va-f and VIa-f) were synthesized and evaluated for their antibacterial and antifungal activities against Staphylococcus aureus (ATCC 25923), methicillin resistant S. aureus (MRSA ATCC 43300), methicillin resistant S. aureus (MRSA isolate), and Escherichia coli (ATCC 23556) and C. albicans (ATCC10145). All the compounds were found active against used microorganisms.     

Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides

N(1)-Phenyl-3,5-dinitro-N(4),N(4)-di-n-propylsulfanilamide (1) and N(1)-phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. Nine of the sulfonamides display in vitro IC(50) values under 500 nM against African trypanosomes, and the most active antikinetoplastid compounds also inhibit the in vitro assembly of purified leishmanial tubulin with potencies similar to that of 2. While several of the potent compounds are rapidly degraded by rat liver S9 fractions in vitro, N(1)-(3-hydroxy)phenyl-3,5-dinitro-N(4),N(4)-di-n-butylsulfanilamide (21) displays an IC(50) value of 260 nM against African trypanosomes in vitro and is more stable than 2 in the in vitro metabolism assay.     

Allicin and derivates are cysteine protease inhibitors with antiparasitic activity

Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2, rhodesain, cathepsin B and L in the low micromolar range. The structure–activity relationship revealed that only derivatives with primary carbon atom in vicinity to the thiosulfinate sulfur atom attacked by the active-site Cys residue are active against the target enzymes. Some compounds also show potent antiparasitic activity against Plasmodium falciparum and Trypanosoma brucei brucei.     

Effect of antimitotic drugs on tubulin GTPase activity and self-assembly.

Microtubule inhibitors can be classified into two categories: 1) those which inhibit the polymerization-dependent GTPase activity of phosphocellulose-purified tubulin, but induce a significant polymerization-independent GTPase activity (e.g. colchicine, griseofulvine, daunorubicine); 2) those which inhibit the GTPase activity associated with tubulin polymerization and that induced by inhibitors of the first class (e.g. the vincaalkaloids and podophyllotoxin). The colchicine-stimulated GTPase activity of tubulin appears to be due to the tubulin.colchicine complex. This suggests that colchicine inhibits tubulin assembly by binding to a tubulin-tubulin interaction site required for the polymerization-dependent GTPase activity and induces by itself a tubulin conformational change that leads to polymerization-independent GTPase activity. Stoichiometry of inhibition by vinblastine of the colchicine-stimulated GTPase activity is 1:2. On the other hand, the inhibition by vinblastine of the tubulin self-assembly and of the polymerization-dependent GTPase activity is strongly substoichiometric at the beginning of the polymerization reaction, 1 vinblastine molecule inhibiting the ability of 10 tubulin dimers to polymerize and to hydrolyze the GTP. However, at the polymerization plateau, the inhibition effect by vinblastine appears to be lower, suggesting a selective action of vinblastine on the early stages of the polymerization reaction.     

Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives

In our present research, we synthesised new thiazolidine-2,4-diones (12–28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC₅₀ values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC₅₀ values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.     

6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity

Acyclic nucleoside phosphonate derivatives containing a pyrimidine base preferably bearing amino groups at C-2 and C-4 (DAPym), and linked at the C-6 position to (S)-[3-hydroxy-2-(phosphonomethoxy)propoxy] (HPMPO), 2-(phosphonomethoxy) ethoxy (PMEO) or (R)-[2-(phosphonomethoxy)propoxy] (PMPO), display an antiviral sensitivity spectrum that closely mimic that of the parental (S)-HPMP-, PME- and (R)-PMP-purine derivatives. Several PMEO-DAPym derivatives proved as potent as PMEA (adefovir) and (R)-PMPA (tenofovir) in inhibiting Moloney murine sarcoma virus (MSV)-induced tumor formation in newborn NMRI mice. The HPMPO-, PMEO- and PMPO-DAPym derivatives represent a novel well-defined subclass among the acyclic nucleoside phosphonates endowed with potent and selective antiviral activity.     

Synthesis and insecticidal activity of fluorinated 2-(2,6-dichloro-4-trifluoromethylphenyl)-2,4,5,6-tetrahydrocyclopentapyrazoles

A number of fluorinated 1-aryl-tetrahydrocyclopentapyrazoles were synthesized and their insecticidal activity was evaluated. Some of the fluorinated compounds had significant insecticidal properties.     

Screening of phytotoxicity of Alternaria macrospora MKP1 against Parthenium hysterophorus L.

Parthenium hysterophorus L. an exotic, pernicious weed is considered as one of the most troublesome weeds for agricultural sector by virtue of its high ecological amplitude and adaptability. Microbes and their by-products are now proved to be a worthy alternative to toxic chemicals used for weed management. Alternaria macrospora MKPI was isolated from the parthenium leaves infected with leaf blight and found pathogenic to the weed. The herbicidal potential of cell free culture filtrate of A. macrospora MKP1 has been tested against parthenium by employing detached leaf bioassay and seed germination bioassay and a significant damage was exhibited by the cultural filtrate of pathogen to the parthenium leaves and seeds.     

Synthesis and antimitotic activity of novel 2-methoxyestradiol analogs. Part III

The syntheses and antimitotic activity of several novel analogs of 2-methoxyestradiol are described. Structural modifications include ring-D homologation, aromatization of the six-membered ring-D to a chrysine type molecule, and introduction of unsaturation in five-membered ring-D along with substitution of alkyl and ethynyl groups for the 17beta-hydroxy function. Of nine analogs synthesized, five have demonstrated superior antiproliferative activities compared to 2-methoxyestradiol.     

Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles

A number of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles were synthesized and evaluated for their antiproliferative activities. The panel substitution included alkyl, aryl, and morpholinoalkyl derivatives. The structures of compounds were identified from elemental, IR, (1)H NMR, (13)C NMR and MS spectra analyses. The cytotoxicity in vitro against the four human cell lines: SW707 (rectal), HCV29T (bladder), A549 (lung), and T47D (breast) was determined. Alkyl and morpholinoalkyl derivatives exhibited significantly lower effect than phenyl ones. The highest antiproliferative activity was found for 2-(2,4-dichlorophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole, with ID(50) two times lower (SW707, T47D) than for cisplatin studied comparatively as the control compound.     

Diversity and antimitotic activity of taxol-producing endophytic fungi isolated from Himalayan yew

Endophytic fungi represent an under explored resource of novel lead compounds and have the capacity to produce diverse classes of plant secondary metabolites. Here, we investigated the endophytic fungal diversity of taxol-producing endophytes from Taxus baccata L. ssp. wallichiana (Zucc.) Pilger and also tested the antimitogenic effect of fungal taxol using potato disc tumor assay. A total of 60 fungal endophytes were isolated from the inner bark (phloem-cambium) of T. baccata ssp. wallichiana, collected from different locations of the northern Himalayan region. Two key genes, DBAT (10-deacetylbaccatin III-10-O-acetyl transferase) and BAPT (C-13 phenylpropanoid side chain-CoA acyltransferase), involved in taxol biosynthesis were used as molecular markers for the screening of taxol-producing strains. Five representative species gave positive amplification hits by molecular marker screening with the bapt gene. These fungi were characterized and identified based on morphological and molecular identification. The taxol-producing capability of these endophytic fungi was validated by HPLC-MS. Among the five taxol-producing fungi, the highest yield of taxol was found to be 66.25 μg/l by Fusarium redolens compared with those of the other four strains.