Provided are a class of vancomycin derivatives with a structure as shown in the general formula below and pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition containing the compound thereof, and the use of these compounds in preparing drugs for treating and/or preventing bacterial infection diseases, in particular drugs for treating infection diseases caused by Gram-positive bacteria. ##STR00001##

Microorganisms are prolific producers of natural products, a group of molecules that make up the majority of drugs approved by the FDA in the past 35 years. After decades of mining, the low-hanging fruit has been picked and so discovery of drug-like molecules from microorganisms has come to a near-halt. The reason for this lack of productivity is that most biosynthetic pathways that give rise to natural products are not active under typical laboratory growth conditions. These so-called cryptic or silent pathways are a major source of new bioactive molecules and methods that reliably activate them could have a profound impact on drug discovery. Disclosed herein is a rapid genetics-free method for eliciting and detecting cryptic metabolites using an imaging mass spectrometry-based approach. An organism of choice is challenged with elicitors from a small molecule library. The molecules elicited are then imaged by mass spec, which allows for rapid identification of cryptic metabolites. These are then isolated and characterized. Employing the disclosed approach activated production of cryptic glycopeptides from an actinomycete bacterium. The molecules that result, the keratinimicins and keratinicyclins, are metabolites with important structural features. At least two of these, keratinimicins B and C, are highly bioactive against several pathogenic strains. This approach will allow for rapid activation and identification of cryptic metabolites from diverse microorganisms in the future.

A C-terminus modification to a binding pocket-modified vancomycin introduces a quaternary ammonium salt that provides a binding pocket-modified vancomycin analog with a second mechanism of action that is independent of D-Ala-D-Ala/D-Ala-D-Lac binding. The modification disrupts cell wall integrity and induces cell wall permeability complementary to the glycopeptide inhibition of cell wall synthesis, and provides synergistic improvements in antimicrobial potency (200-fold) against vancomycin-resistant bacteria. Combining the C-terminus and binding pocket modifications with an orthogonal (4-chlorobiphenyl) methyl addition to the vancomycin disaccharide provides even more potent antimicrobial agents whose activity can be attributed to three independent and synergistic mechanisms of action, only one of which requires D-Ala-D-Ala/D-Ala-D-Lac binding. The resulting modified vancomycins display little propensity for acquired resistance through serial exposure of vancomycin-resistant Enterococci and their durability against such challenges as well as their antimicrobial potency follow predicable trends. Methods of treatment with and compositions containing the modified vancomycins are disclosed.

The present disclosure relates to novel antibacterial cell-penetrating peptides and derivatives, and methods to make and use the novel antibacterial cell-penetrating peptides and derivatives. The novel antibacterial cell-penetrating peptides of the present invention with shorter linker between a pyrrolidine ring and a guanidine group provide unexpectedly higher potency against a broader scope of bacterial.

Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.

Provided herein are methods and compositions for the treatment of Gram positive bacterial infections. The infection in some embodiments, is a pulmonary infection. The method for treating the bacterial infection, comprises in one embodiment, administering to a patient in need thereof, a composition comprising an effective amount of a compound a glycopeptide derivative of Formula (I) or (II), or a pharmaceutically acceptable salt of Formula (I) or (II).

The object of the invention is a porous alumina ceramic matrix grafted with an antibiotic, in particular vancoymicin, as well as its use in therapy. The invention also relates to a prosthesis or an implant using this matrix. The invention also relates to a method for preparing a matrix according to the invention.

Disclosed herein are novel compounds and uses thereof. The present compounds are useful in suppressing the growth of various bacteria, including gram-positive and gram-negative bacteria. Accordingly, these compounds may be used to manufacture a medicament or pharmaceutic composition for treating disease and/or disorders associated with bacterial infection, especially antibiotic-resistant bacterial infection. Al so disclosed herein are methods for treating infectious diseases by use of the present compounds, medicament or pharmaceutical composition.

Some embodiments of the disclosure provide a time-resolved fluorescent immunochromato-graphic test strip for detecting vancomycin as well as a preparation method and application thereof. In some embodiments, the test strip includes a bottom plate and a sample absorption pad. A fluorescent microsphere pad, a nitrocellulose membrane coated with a vancomycin-carrier protein conjugate, and an absorbent pad are sequentially overlapped and pasted on the bottom plate. The fluorescent microsphere pad is sprayed with a fluorescent microsphere-labeled vancomycin monoclonal antibody, and the vancomycin monoclonal antibody is prepared by using a vancomycin-bovine serum albumin conjugate as an immunogen.

The present disclosure relates to novel antibacterial cell-penetrating peptides and derivatives, and methods to make and use the novel antibacterial cell-penetrating peptides and derivatives. The novel antibacterial cell-penetrating peptides of the present invention with shorter linker between a pyrrolidine ring and a guanidine group provide unexpectedly higher potency against a broader scope of bacterial.