Pyrazinoic acid and its n-propyl ester inhibit fatty acid synthase type I in replicating tubercle bacilli.

نویسندگان

  • Oren Zimhony
  • Catherine Vilchèze
  • Masayoshi Arai
  • John T Welch
  • William R Jacobs
چکیده

The activity of different analogs of pyrazinamide on Mycobacterium tuberculosis fatty acid synthase type I (FASI) in replicating bacilli was studied. Palmitic acid biosynthesis was diminished by 96% in bacilli treated with n-propyl pyrazinoate, 94% in bacilli treated with 5-chloro-pyrazinamide, and 97% in bacilli treated with pyrazinoic acid, the pharmacologically active agent of pyrazinamide. We conclude that the minimal structure of pyrazine ring with an acyl group is sufficient for FASI inhibition and antimycobacterial activity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Inhibition of isolated Mycobacterium tuberculosis fatty acid synthase I by pyrazinamide analogs.

An analog of pyrazinamide (PZA), 5-chloropyrazinamide (5-Cl-PZA), has previously been shown to inhibit mycobacterial fatty acid synthase I (FASI). FASI has been purified from a recombinant strain of M. smegmatis (M. smegmatis Deltafas1 attB::M. tuberculosis fas1). Following purification, FASI activity and inhibition were assessed spectrophotometrically by monitoring NADPH oxidation. The observe...

متن کامل

Effects of pyrazinamide on fatty acid synthesis by whole mycobacterial cells and purified fatty acid synthase I.

The effects of low extracellular pH and intracellular accumulation of weak organic acids were compared with respect to fatty acid synthesis by whole cells of Mycobacterium tuberculosis and Mycobacterium smegmatis. The profile of fatty acids synthesized during exposure to benzoic, nicotinic, or pyrazinoic acids, as well as that observed during intracellular hydrolysis of the corresponding amides...

متن کامل

Effects of weak acids, UV and proton motive force inhibitors on pyrazinamide activity against Mycobacterium tuberculosis in vitro.

BACKGROUND Pyrazinamide is a paradoxical frontline tuberculosis drug characterized by high sterilizing in vivo activity but poor in vitro activity. Pyrazinamide is thought to act by the entrapment of pyrazinoic acid in the bacterial cell, leading to acidification and membrane damage. Consequently, the effects of weak acids and molecules affecting membranes added to pyrazinamide were studied. ...

متن کامل

The Effect of Wetting Agents on the Growth of Tubercle Bacilli

Tween 80 and Triton A20 are two water-dispersible, non-ionic, surface-active agents which favor dispersed growth of tubercle bacilli in aqueous media probably by wetting the bacterial surface. Tween 80 is a polyoxyethylene ester of sorbitan monooleate and is liable to enzymatic hydrolysis by lipases. Triton A20 in an arylalkyl polyether of phenol which appears resistant to the known enzymes of ...

متن کامل

ONE STEP SYNTHESIS OF ANILINO ALKYL-NSUBSTITUTED PHTHALIMIDES RELATED TO BENZOISOQUINOLINE-1,3-DIONES (1)

A facile one step synthesis of anilino alky1-N-substituted phthalimide I is reported. The following compounds belonging to this series were made: 1. (anilino-N-ethyl) phthalimide 8 2. (3,4, 5-trimethoxy anilino-N-ethyl) phthalimide 6 3. (3,4, 5-trimethoxy anilino-N-propyl) phthalimide 7 4. N-(ethyl phthalirnido-p-amino benzoyl) glutamic acid diethyl ester 10 5. N-(propyl phthalimido-p-ami...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 51 2  شماره 

صفحات  -

تاریخ انتشار 2007