827306-59-2Relevant academic research and scientific papers
Design and Synthesis of Pyrophosphate-Targeting Vancomycin Derivatives for Combating Vancomycin-Resistant Enterococci
Guan, Dongliang,Chen, Feifei,Faridoon,Liu, Junjie,Li, Jian,Lan, Lefu,Huang, Wei
, p. 1644 - 1657 (2018)
As the last resort for intractable Gram-positive bacterial infections, vancomycin is losing efficacy with the emergence of vancomycin-resistant bacteria, especially vancomycin-resistant Enterococci (VRE). To combat this threat, we rationally designed and synthesized 39 novel vancomycin derivatives by respective or combined modifications using metal-chelating, lipophilic, and galactose-attachment strategies for extensive structure–activity relationship (SAR) analysis. In a proposed mechanism, the conjugation of dipicolylamine on the seventh amino acid resorcinol position or C-terminus endowed the vancomycin backbone with binding capacity for the pyrophosphate moiety in lipid II while maintaining the intrinsic binding affinity for the dipeptide terminus of the bacterial cell wall peptidoglycan precursor. The in vitro antibacterial activities were evaluated, and the optimal compounds indicated 16- to 1024-fold higher activity against VRE than that of vancomycin. Compound 11 b (3′,5′-bis(dipicolylaminomethyl)tyrosine [1,2,3]triazolylmethoxylethyoxyl ethylaminomethyl-N-decylvancomycin) was found to have particularly potent activity against VRE through synergistic effects brought about by combining two peripheral modifications.
Organometallic 99mTc-technetium(I)- and Re-rhenium(I)-folate derivatives for potential use in nuclear medicine
Müller, Cristina,Dumas, Cécile,Hoffmann, Ute,Schubiger, P. August,Schibli, Roger
, p. 4712 - 4721 (2004)
The folate receptor (FR) is a high affinity membrane protein which is overexpressed on a wide variety of tumor cells, but highly restricted in normal tissues. Therefore folate derivatives labeled with short living isotopes such as 99mTc (γ, t1/2 = 6 h) or 188Re (β-, t1/2 = 17 h) could be used for tumor diagnosis and therapy. In this respect there is a great interest to develop organometallic technetium(I) and rhenium(I) modified folate radiopharmaceuticals. For this purpose folic acid was functionalized with a tridentate picolylamine monoacetic acid chelating system. The chelating system was selectively coupled via an aminohexane spacer to the γ- or α-carboxyl group of the glutamate moiety of folic acid to obtain the corresponding γ- or α-folate derivative or - if directly attached to pteroic acid - the pteroate derivative. The derivatives were reacted with the precursor [M(OH2) 3(CO)3]+ (M = 99mTc, Re) to form uniform organometallic folate complexes under mild reaction conditions. All compounds were chemically characterized by means of NMR, MS, IR and HPLC. The determination of the IC50-values for the PAMA-γ-folate derivative (100 nM) and the corresponding organometallic rhenium complex (110 nM) proved retained receptor binding properties. The radiolabeling with [ 99mTc(OH2)3(CO)3]+ was achieved in excellent yield (>95%) at low ligand concentration (10 -4 M). The cell binding (>45% of total activity) and internalization (>15% of total activity) of all 99mTc-complexes was very high and specificity for the FR was proved by their complete displacement with excess folic acid. The 99mTc-complexes were positively tested for their plasma stability and for the absence of binding to plasma proteins.
GLYCOPEPTIDES CONJUGATES AND USES THEREOF
-
Paragraph 000178; 000179, (2016/09/22)
Vancomycin conjugates of Formula I, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complexes thereof is described in the present disclosure. Further, the present disclosure relates to pharmaceutical compositions comprising vancomycin conjugates, its stereoisomers, prodrugs, pharmaceutically 10 acceptable salts, metal coordination complex thereof with one or more other pharmaceutical compositions or an antibiotic. The present disclosure also describes a process of preparing said conjugates, its stereoisomers, prodrugs, pharmaceutically acceptable salts, and metal coordination complex thereof, and pharmaceutical compositions as described above. Furthermore, the present disclosure describes 15 compositions and methods of treating conditions and diseases that are mediated by bacteria
