Abstract
The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure–activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1.
Highlights
Tuberculosis, caused by Mycobacterium tuberculosis, remains a major infectious disease worldwide
One of the major reasons for the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to remain in a dormant state [3]
We evaluate the function of the compound having a photoaffinity group and exhibiting antimicrobial activity as a probe molecule
Summary
Tuberculosis, caused by Mycobacterium tuberculosis, remains a major infectious disease worldwide. 10 million cases of tuberculosis and 1.5 million deaths globally [1]. The regimen administers isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and rifampicin for 4 months, and is highly effective against the drug-susceptible M. tuberculosis [2]. One of the major reasons for the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to remain in a dormant state [3]. Only three new anti-tuberculosis drugs, bedaquiline (TMC207), delamanid (OPC-67683), and pretomanid (PA-824), have been developed and approved in the past 50 years. There already exist several cases that are resistant to both bedaquiline and delamanid treatment [4,5]
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