Propylene tethered ciprofloxacin-isatin hybrids as well as synthetic method and application thereof

Abstract

The invention discloses propylene tethered ciprofloxacin-isatin hybrids as well as a synthetic method and an application thereof. The prepared ciprofloxacin-isatin hybrid 3d have strong resistance toall tested Gram-positive bacteria and Gram-negative bacteria (including pathogens showing strong drug resistance clinically), and efficacy of 3d is equivalent to or even better than the parent ciprofloxacin or levofloxacin; antibacterial activity of hybrid 3b (MIC: 0.10 and 0.5 mu g / mL) for an mycobacterium tuberculosis H37Rv strain is 4 times and 8 times that of ciprofloxacin (MIC: 0.78 mu g / mL)and rifampicin (MIC: 0.39 mu g / mL), and antibacterial activity of the hybrid 3b for multi-drug resistant tuberculosis is 4->256 times that of three reference drugs including ciprofloxacin (MIC: 2.0 mug / mL), rifampicin (MIC: 32 mu g / mL) and isoniazid (>128 mu g / mL). The hybrids 3b and 3d with lower cytotoxicity (CC50: 64 and 256 mu g / mL) show acceptable metabolic stability and in-vivo PK (pharmacokinetics) characteristics.

Description

technical field [0001] The patent belongs to the field of medicinal chemistry, and in particular relates to a propylene tethered ciprofloxacin-indolindione hybrid compound and its synthesis method and application. Background technique [0002] Bacterial infections caused by gram-positive and gram-negative bacteria, as well as mycobacterial pathogens, are the leading cause of hospital-acquired infections, resulting in a large number of deaths and imposing an enormous burden on healthcare systems worldwide. The latest report from the World Health Organization (WHO) estimates that approximately 10 million people die from infectious diseases each year (accounting for more than 15% of all deaths), and that tuberculosis (TB) is the ninth leading cause of death globally and is also the result of a single infection. source of the main reason. In recent years, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomy...

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Problems solved by technology

[0004] However, like other types of antimicrobials, bacterial pathogens develop resistance to fluoroquinolones rapidly, and the main reason for this serious situation is due to the long-term, widespread, inappropriate use and even abuse of these drugs , which makes it less and less effective in the treatment of bacterial infections

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