Provided herein are apohemoglobin-haptoglobin complexes as well as apohemoglobin-haptoglobin complexes comprising an active agent coordinated thereto. Methods of using these compositions are also described.

Disclosed herein are dual drug antibody drug conjugates with defined stoichiometric ratios of each drug. The conjugates disclosed herein are useful for the treatment of cancer, particularly drug resistant and multidrug resistance cancer.

A conjugate provided. The conjugate is a compound represented by Formula (I), or the conjugate is a stereoisomer, tautomer, homologue, solvate, metabolite, pharmaceutically acceptable salt, or prodrug of the compound represented by Formula (I):

##STR00001##

where A is a linker, and B is a dihydrofolate reductase inhibitor; R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are independently selected from H or C.sub.1-6 alkyl; and n1, n2, and n3 are each an integer selected from 0 to 6.

The present application relates to novel 3-imidazolines of formula (I′) and (I) below: (I′) (I) Wherein Ar.sub.1, Ar.sub.2, Ar.sub.3, and R.sub.1 to R.sub.6 are as defined in the claims. The 3-imidazolines of the invention are useful in antibiotic therapies, in particular as inhibitors of carbapenemases. They are also useful as antibiotics themselves. The present invention also concerns a method for preparing more specifically the 3-imidazolines of formula (I). The present invention further relates to conjugates of said compounds with known antibiotics. ##STR00001##

The present invention provides an application of a rifamycin-quinolizidone conjugate molecule shown in formula I and pharmaceutically acceptable salt thereof in preparation of a drug for treating or preventing infections caused by methicillin-resistant, quinolone-resistant, and methicillin and quinolone multidrug resistant Staphylococcus aureus. The rifamycin-quinolizidone conjugate molecule and pharmaceutically acceptable salt thereof provided by the present invention can effectively treat or prevent bacterial infections and diseases caused by methicillin-resistant, quinolone-resistant, and methicillin and quinolone multidrug resistant Staphylococcus aureus, and can reduce spontaneous resistance frequency as compared with a drug combination of rifamycin and quinolones.

##STR00001##

Disclosed herein is an attenuated Acinetobacter baumannii comprising an expression vector comprising a nucleic acid encoding the ABUW_1645 protein or a variant thereof. Disclosed herein are methods of treating or preventing colonization, infection, or disease by an Acinetobacter baumannii microbe, the method comprising administering a clinically effective dose of the attenuated Acinetobacter baumannii to a subject in need thereof, wherein the attenuated Acinetobacter baumannii comprises an expression vector expressing the ABUW_1645 protein or variants thereof.

Provided are antibiotic conjugate compounds of formula (I) and pharmaceutical compositions thereof. Also provided are methods of treating treat bacterial infection, including infections caused by Gram-negative bacteria, by administering compounds of formula (I).

##STR00001##

The subject invention pertains to polyacrylate homopolymers produced from acrylolated drug monomers. The homopolymers can be produced in the form of nanoparticles. The nanoparticles comprising the homopolymers can be produced via a free radical-induced emulsion polymerization of the acrylolated drug monomers to produce an aqueous emulsion of uniformly sized nanoparticles. The homopolymers of the invention containing acrylolated antibiotic monomers can be active against Gram-positive and Gram-negative bacteria, such as Staphylococcus aureus and Escherichia coil. Accordingly, methods are provided of treating a disease, for example, an infection, by administering to a subject the homopolymers, homopolymeric nanoparticles, or emulsions containing homopolymeric nanoparticles of the invention.

Described herein are bisphosphonate quinolone compounds, conjugates and pharmaceutical formulations thereof that can include a bisphosphonate and a quinolone, where the quinolone can be releasably coupled to the bisphosphonate. Also provided herein are methods of making and methods of using the bisphosphonate quinolone compounds, conjugates and pharmaceutical formulations thereof.

The present invention relates to conjugates of aminoglycosides and terpenoids, in particular sesquiterpenoids. Furthermore, the present invention relates to nano-assemblies formed by the inventive conjugates and to a method for producing the conjugates and/or the nano-assemblies. The present invention also relates to the inventive conjugates and nano-assemblies for use in therapy, in particular for use in the treatment of infectious diseases. Particularly preferred embodiments of the present invention relate to farnesylated aminoglycosides and nano-assemblies thereof, in which farnesol and its derivatives do not only function as carrier for the aminoglycosides but do themselves have pharmaceutical activity upon cleavage of the conjugate, in particular quorum sensing inhibitory activity.