Yun Chai

Synthesis and in vitro antimycobacterial activity of balofloxacin ethylene isatin derivatives.

A series of novel balofloxacin ethylene isatin derivatives with remarkable improvement in lipophilicity, as compared to the parent compound balofloxacin, were designed, synthesized and characterized by (1)H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. phlei CMCC 93201 and M. smegmatis CMCC 93202. Compounds 3b, 3d, 3g-j and 3l were chosen for further evaluation their in vitro activity against MTB 09710 clinical isolate, and then compounds 3h and 3g against MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than balofloxacin against M. phlei CMCC 93201 and M. smegmatis CMCC 93202, but compounds 3g-j (MIC: <0.5-8 microg/mL) were more potent than balofloxacin (MIC: 16 microg/mL) against MTB 09710. In particular, compound 3h (MIC: 0.25- < 0.5 microg/mL) was found to be comparable to moxifloxacin, and >or=32 fold more potent than balofloxacin against MTB 09710 and MTB H37Rv ATCC 27294. The results demonstrated that the lipophilicity of the tested compounds was not the sole parameter affecting antimycobacterial activity, as well as the potential and importance of developing new fluoroquinolone derivatives against mycobacterial infections.

Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl) fluoroquinolone derivatives.

A series of novel 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cytotoxicity. All of the target compounds have potent antibacterial activity against the tested Gram-positive and Gram-negative strains, and exhibit good potency in inhibiting the growth of Staphylococcus aureus including MRSA, Staphylococcus epidermidis including MRSE and Streptococcus pneumoniae (MICs: 0.125-4 μg/mL). Compound 22, with the best activity against Gram-positive strains, is 4-16 fold more potent than gemifloxacin, gatifloxacin and levofloxacin against Enterococcus faecalis, and 16- and 4-fold more potent than levofloxacin against S. epidermidis 09-6 and S. pneumoniae 08-4, respectively.

Synthesis and in vitro antibacterial activity of novel fluoroquinolone derivatives containing substituted piperidines

We report herein the synthesis of novel 7-(4-alkoxyimino-3-aminomethyl-3-methylpiperidin-1-yl) fluoroquinolone derivatives. The antibacterial activity of the newly synthesized compounds was evaluated and correlated with their physicochemical properties. Results reveal that all of the target compounds have good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis including MRSE (MIC: 0.125-4 microg/mL). Compounds 12, 13 are more potent than or comparable to levofloxacin against MRSA, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Shigella sonnei. Compound 17 is more active than or comparable to levofloxacin against S. aureus including MRSA, S. epidermidis and S. pyogenes.

Synthesis and In Vitro Antimycobacterial and Antibacterial Activity of 8-OMe Ciprofloxacin-Hydrozone/Azole Hybrids

A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. Our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against Mycobacterium tuberculosis (MTB) H37Rv (minimum inhibitory concentration (MIC): <0.5 μM), which is better than the parent drug CPFX, and comparable to moxifloxacin and isoniazid, some of the tested Gram-positive strains (MIC: 0.06–4 μg/mL), and most Gram-negative strains (MIC: ≤0.03–4 μg/mL).

Design, synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-aminomethylpiperidin-1-yl)fluoroquinolone derivatives.

We report herein the design and synthesis of novel 7-(4-alkoxyimino-3-aminomethylpiperidin-1-yl) fluoroquinolone derivatives. The antibacterial activity of the newly synthesized compounds was evaluated and compared with gemifloxacin, levofloxacin and ciprofloxacin. Results reveal that compounds 10, 16, and 17 have good activity against all of the tested gram-positive organisms including drug-resistance strains (MICs: 0.125-4 μg/mL). In addition, compounds 16 and 17 (MICs: 4 μg/mL) were 2- to 8-fold more potent than the reference drugs against Pseudomonas aeruginosa.

Identification of Better Pharmacokinetic Benzothiazinone Derivatives as New Antitubercular Agents

A series of new 8-nitro-6-(trifluoromethyl)-1,3-benzothiazin-4-one(BTZ) derivatives containing a C-2 nitrogen spiro-heterocycle moiety based on the structures of BTZ candidates BTZ043 and PBTZ169 were designed and synthesized as new antitubercular agents. Many of them were found to have excellent in vitro activity (MIC < 0.15 μM) against the drug susceptive Mycobacterium tuberculosis H37Rv strain and two clinically isolated multidrug-resistant strains. Compounds 11l and 11m display acceptable safety, greater aqueous solubility, and better pharmacokinetic profiles than PBTZ169, suggesting their promising potential to be lead compounds for future antitubercular drug discovery.

Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide-releasing moiety

A series of novel ATB-429 (an anti-inflammatory candidate) derivatives containing a nitric oxide (NO)-releasing moiety were designed, synthesized and evaluated for their in vitro activity against six human cancer cell lines. Our results reveal that phenylsulfonylfuroxan-based derivatives have considerable antitumor activity, and compounds 7-9 (IC50s: 0.256-3.024 μM) against HT-29 and PANC-1, 8a,b (IC50s: 2.677-3.051 μM) against MCF-7 and 8a (IC50: 1.270 μM) against DU145 are more active than Vandetanib (IC50s: 1.925-4.107 μM).

Synthesis and Antitumor Activity of 5-Bromo-7-azaindolin-2-one Derivatives Containing a 2,4-Dimethyl-1H-pyrrole-3-carboxamide Moiety

We report herein the design and synthesis of a series of novel 5-bromo-7-azaindolin-2-one derivatives containing a 2,4-dimethyl-1H-pyrrole-3-carboxamide moiety. These newly synthesized derivatives were evaluated for in vitro activity against selected cancer cell lines by MTT assay. Results revealed that some compounds exhibit broad-spectrum antitumor potency, and the most active compound 23p (IC50: 2.357–3.012 μM) was found more potent than Sunitinib (IC50: 31.594–49.036 μM) against HepG2, A549 and Skov-3, respectively.

tert-Butyl 3-carbamoyl-4-methoxy-imino-3-methyl-piperidine-1-carboxyl-ate.

In the title compound, C13H23N3O4, the piperidine ring adopts a chair conformation. An intramolecular N—H⋯O hydrogen bond is observed between the carbamoyl and carboxylate groups. In the crystal structure, molecules form inversion dimers linked by pairs of N—H⋯O hydrogen bonds.

N-(4-Hydroxy­pheneth­yl)acetamide

In the title compound, C10H13NO2, the occurrence of intermolecular N—H⋯O and O—H⋯O hydrogen bonds between the hydroxy and acetamido groups results in the formation of tetramers with an R 4 4(25) graph-set motif. These tetramers are further assembled, building up a corrugated sheet parallel to (001).