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Pharmaceutical compounds comprise a widely employed group of therapeutic agents now considered as emerging micropollutants. This chapter summarizes the state of the art in the degradation of pharmaceuticals by fungi in liquid matrices (with emphasis on white-rot fungi), including the use of both whole cells and fungal enzymes. The identification of the metabolites produced as well as the proposed degradation pathways available for some drugs are discussed. The information is organized according to the activity of the pharmaceutical compounds, grouped in: anti-inflammatory/analgesic drugs, psychiatric drugs, lipid regulators, antibiotics and other antimicrobial agents, beta-blockers, estrogens, and iodinated contrast media. Considering the interest in potential application of fungal treatments in future real scale bioremediation of effluents, the ecotoxicology of the process is included when available.

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Reference:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Certain substituted urea derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Microalgae-mediated biodegradation of antibiotics has recently gained increased attention from international scientific community. However, limited information is available regarding microalgae-mediated biodegradation of SMX in a co-metabolic system. Here we investigated the biodegradation of sulfamethoxazole (SMX) by five algal species (Pseudokirchneriella subcapitata, Scenedesmus quadricauda, Scenedesmus obliquus, Scenedesmus acuminatus and Chlorella pyrenoidosa), and its transformation pathways by C. pyrenoidosa in a sodium acetate (3 mM) co-metabolic system. The results showed that the highest SMX dissipation (14.9%) was detected by C. pyrenoidosa after 11 days of cultivation among the five tested algal species in the absence of other carbon sources. The addition of sodium acetate (0?8 mM) significantly enhanced the dissipation efficiency of SMX (0.4 muM) from 6.05% to 99.3% by C. pyrenoidosa after 5 days of cultivation, and the dissipation of SMX followed the first-order kinetic model with apparent rate constants (k) ranging from 0.0107 to 0.9811 d?1. Based on the results of mass balance analysis, biodegradation by C. pyrenoidosa was the main mechanism for the dissipation of SMX in the culture medium. Fifteen phase I and phase II metabolites were identified, and subsequently the transformation pathway was proposed, including oxidation, hydroxylation, formylation and side chain breakdown, as well as pterin-related conjugation. The majority of metabolites of SMX were only observed in the culture medium and varied with cultivation time. The findings of the present study showed effective co-metabolism of a sulfonamide by microalgae, and it may be applied in the aquatic environment remediation and wastewater treatment in the future.

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A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2 muM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer.

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Ethyl(Z)-2-<2,2-bis(ethoxycarbonyl)vinyl>amino-3-dimethylaminopropenoate(5), a new reagent in the synthesis of heteroaryl substituted beta-amino-alpha,beta- -dehydro-amino acid derivatives and some fused heterocyclic systems, was prepared from ethyl N-2,2-bis(ethoxycarbonyl)vinylglycinate (3) and N,N-dimethylformamide dimethyl acetal (4).The substitution of the dimethylamino group in the compound 5 with heterocyclic amines produced ethyl 2-<2,2-bis(ethoxycarbonyl)vinyl>amino-3-heteroarylaminopropenoates 7a-f and in some instances, <2,2-bis-(ethoxycarbonyl)vinyl>aminoazolo- or-azinopyrimidine derivatives 8g-k.

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The rate constants of sulfamethoxazole (SMX) and ciprofloxacin (CIP) degradation as well as the removal of total organic carbon (TOC) by UV/H2O2 process was investigated under various parameters including different H2O2 dosage and initial pH values. The results indicated that both SMX and CIP were efficiently removed in UV/H2O2 process and they peaked at different pH values of 3 and 7 respectively, while CIP degradation was greater than that of SMX. TOC removal was decreased with the pH values increased in the degradation of SMX in UV/H2O2 process while no significant change for CIP with the pH values raised. Based on molecular structure analysis, the transformation of both sulfonamide bond and oxazole ring N?O band in SMX were more difficult than defluorination and change of piperazine ring in CIP.

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The reactions of 3-cyano-4-chlorocoumarin (1) with 2-amino-5-chlorobenzoxazole (2), 3-amino-5-methylisoxazole (3) and 2-amino-1,3,4-thiadiazole (4) have been investigated. Novel heterocyclic ring systems, namely 7-imino-10-chlorobenzoxazolo[1,2-b] pyrimido – [4,5:4′,3′] 6H,7H[1]-benzopyrano-6-one (5), 3-cyano-4-(3-amino-5-methylisoxazolo)-coumarin (6) and 7-imino [2,3-a] thiadiazolo[4′,3′:3,4] pyrimido 6H,7H [1]-benzopyrano-6-one (7) were synthesized and characterized on the basis of spectral and analytical data. Their structures were supported by simple chemical transformation.

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A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.

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A compound of formula (I), useful for the treatment of cancer, inflammation and inflammatory disorders, and a pharmaceutical composition containing the compound.

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Reference:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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A series of 1,2-dihydro-1-oxopyrrolo<3,2,1-kl>phenothiazine, 1,2-dihydro-1-oxopyrrolo<3,2,1-kl>phenoxazine, and 1,2-dihydro-1-oxopyrrolo<3,2,1-de>acridine-2-carboxamides were prepared by reaction of 1,2-dihydro-1-oxopyrrolo<3,2,1-kl>phenothiazine or other corresponding phenoxazine and acridan ethyl or methyl esters with appropriate amines.Several members of this family were found to be potent, dual inhibitors of cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism and to have in vivo antiinflammatory activity in the rat foot edema assay.Structure-activity relationships within this family of compounds are described. 1,2-Dihydro-N-(2-thiazolyl)-1-oxopyrrolo<3,2,1-kl>phenothiazine-1-carboxamide (34) was found to be one of the best compounds to display potent cyclooxygenase/5-lipoxygenase inhibition of arachidonic acid metabolism.Its IC50s against the enzymes sourced from rat basophillic leukemia-1 (RBL-1) cells were 0.07 and 1.4 muM, respectively.It was active in the rat foot edema test for antiinflammatory effect (48percent inhibition at 33 mg/kg po) and in the mouse phenylbenzoquinone induced writhing test for analgesic effect (93percent inhibition at 32 mg/kg po).

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