The current work is concerned with synthesis of new 1,2,4-traizoles, 1,3,4-thiadiazoles, and 1,3,4-thiadiazines derivatives. Derivatives 3a-i were obtained by condensation of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 with the appropriate aldehyde. Compounds 4a-i were synthesized in a one pot reaction involving compounds 3a-i, formaldehyde and morpholine. Condensation of compound 1 with the appropriate acids 4-substituted phenacyl bromide gave compounds 6a-d and 8a-f respectively. The chemical structures of the newly synthsized derivatives were elucidated using different spectral and elemental methods of analyses. All compounds were evaluated for their anti-inflammatory activity and the most potent derivatives were tested for their analgesic activity using indomethacin as a reference drug. In addition, ulcerogenicity and LD50 for the most active compounds were evaluated. Moreover, The antibacterial activities of the newly synthesized derivatives were investigated.

A series of 1,4-disubstituted octahydroquinoxaline-2,3-dione derivatives was prepared through two steps reaction. The latter involves the formation of N,N-disubstituted cyclohexane-1,2-diamine derivatives (1a-j) through reductive alkylation of 1,2-cyclohexanediamine with different aldehydes in presence of sodium cyanoborohydride. Fusion of compounds (1a-j) with diethyl oxalate affording the target compounds (2a-j). Elucidation of structures of compounds (2a-j) was based upon different spectral data as well as the elemental methods of analyses. In addition, mass spectrometry and X-ray diffraction analyses were carried out. Moreover, the lipophilicity of the target compounds as expressed from the Clog P. Most of the test compounds (2a-j) showed weak to moderate antibacterial and antifungal activities against most of the used bacterial and fungal strains in comparison to chloramphenicol and clotrimazole as reference drugs respectively.

Introduction: Earthworms are the major biomass in soil. They have been widely used in traditional Chinese medicine for a long time. However, in the past few decades with the development of biochemical technologies the research on the pharmaceutical effects of earthworms has been commencement. Aims: Experiments were conducted to recognize the therapeutic properties such as anti-inflammatory, antipyretic and antioxidant activities of biologically active extract isolated from two species of earthworm (Pheretima hawayana Rosa and Allolobophora caliginosa Savigny). Materials and methods: Inflammation in the hind paw of albino rat (Rattus rattus) was induced by histamine, pyrexia was induced by Escherichia coli in rats and liver damage was induced by injection of rats with CCl4. Anti-inflammatory drug - indomethacin, anti-pyretic drug - paracetamol and antioxidant drug - silymarin plus were used as standard drugs for comparison. Results: Administration of earthworms extract (100 mg/kg) and indomethacin (10 mg/kg), paracetamol (150 mg/kg), silymarin plus (150 mg/kg) as standard drugs reduced and restored to normal the changes that induced by histamine, Escherichia coli and CCl4 in rats. Conclusions: The present study conclude that both extracts of earthworms gave result as anti-inflammatory and anti-pyretic similar to the standard drugs. The extract of the two species showed various responds as antioxidants against CCl4 induced hepatotoxicity.

A near-infrared fluorochrome, GPU-311, was designed, synthesized and evaluated for its application in non-invasive imaging of tumor hypoxia. Efficient synthesis was achieved by nucleophilic substitution and click chemistry ring using the bifunctional tetraethylene glycol linker 2 containing thiol and azide groups for the conjugation of the propargylated nitroimidazole 1 and the heptamethine cyanine dye 3 bearing a 2-chloro-1-cyclohexenyl ring. GPU-311 exhibited long excitation and emission wavelength (Ex/Em_785/802 nm) and a decent quantum yield (0.05). The water solubility and hydrophilicity of GPU-311 increased. After in-vitro treatment of SUIT-2/HRE-Luc pancreatic cancer cells with GPU-311, a higher level of fluorescence was observed selectively in hypoxia than in normoxia. However, in-vivo fluorescence imaging of a mouse xenograft model after GPU-311 administration revealed inadequate accumulation of GPU-311 in tumors due to its rapid elimination through the liver.

We developed a novel near-infrared (NIR) fluorescent probe, GPU-167, for in-vivo imaging of tumor hypoxia. GPU-167 comprises a tricarbocyanine dye as an NIR fluorophore and two 2-nitroimidazole moieties as exogenous hypoxia markers that undergo bioreductive activation and then selective entrapment in hypoxic cells. After treatment with GPU-167, tumor cells contained significantly higher levels of fluorescence in hypoxia than in normoxia. In-vivo fluorescence imaging specifically detected GPU-167 in tumors 24 h after administration. Ex-vivo analysis revealed that fluorescence showed a strong correlation with hypoxia inducible factor (HIF)-1 active hypoxic region. These data suggest that GPU-167 is a promising in-vivo optical imaging probe for tumor hypoxia.

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC50 value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC50 value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC50 value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.

A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC50 value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.

The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.