Design, synthesis, molecular docking, and spectral studies of new class of carbazolyl polyhydroquinoline derivatives as promising antibacterial agents with noncytotoxicity towards human mononuclear cells from peripheral blood

Abstract A new class of β-lactam pharmacophore series of 2-Bromo-N-[4-(2-{[2-(substituted phenyl)-3-chloro-4-oxoazetidin-1-yl] amino}-2-oxoethyl) phenyl] pyridine-4-carboxamide derivatives were designed, prepared, and screened for their antimycobacterial activities. The hydrazone derivatives were first synthesized via conventional and microwave methods, and then the β-lactam ring could be constructed via a [2+2] ketenimine cycloaddition. The structure of all synthesized compounds was characterized by FTIR, 1H NMR, 13C NMR, and Mass spectroscopy techniques. All the newly synthesized derivatives were found to be effective in inhibiting M. tuberculosis H37RV strain infection at concentrations of 12.5, 25.0, and 50.0 µg/mL using the MABA method. Amongst, the compound (6e) was found to be good potent antitubercular activity at 12.5 mg/mL concentration in comparison with the rest of the compounds using the standard therapeutic agent Streptomycin. Molecular dynamics simulation studies and Molecular docking studies have been performed against mycobacterial InhA enzyme to gain an insight into the possible mechanistic action in search of good potent antitubercular candidates.

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Effect of some ent -Kaurenes on the Viability of Human Peripheral Blood Mononuclear Cells

Natural Product Communications ◽

10.1177/1934578x1200700503 ◽

2012 ◽

Vol 7 (5) ◽

pp. 1934578X1200700

Author(s):

Yndra Cordero ◽

Grecia M. Corao ◽

José A. Cova ◽

Alfredo Usubillaga

Keyword(s):

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Toxic Compounds ◽

Future Studies ◽

In Vivo Experiments ◽

Human Mononuclear Cells ◽

Low Toxicity

The possible cytotoxic activity of some ent-kaurenes on human mononuclear cells, obtained from peripheral blood, was studied having in mind future studies on their antitumor activity. The cells were obtained using the Ficoll-Hypaque method, adjusted to 2×106cells/mL, and incubated with kaurenes for 48 hours at 3×10-5, 30×10−5, 300×10−5 and 3000×10−5μmol/well. Ent-kaurenic acid showed no toxicity at all concentrations studied. The least toxic of all the kaurene derivatives studied was ent -15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid, with a cellular viability of 99% at 3×10−5μmol/well, and 94% at 30×10−5μmol/well. Another compound that showed low toxicity was the 2,3,4,6-tetra-acetyl-α-D-pyranosyl ester of ent-15-oxo-(-)-kaur-16-en-19-oic acid with 44% viability at 3000×10−5Vmol/well. The most toxic compounds at all concentrations tested were ent-kaur-16-en-19-ol acetate and ent-16α-hydroxy-(-)-kauran-19-oic acid. On the other hand, ent-kaur-9(11)16-dien-19-oic acid, ent-kauran-19-oic acid, and ent-kaur-16-en-19-ol were toxic only at the highest concentration studied. According to these results, and considering the concentrations employed, ent-kaur-16-en-19-oic acid and ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid could be used for in vivo experiments and possibly for therapeutic purposes on humans, without much risk.

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