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1.D.283.  The Azobenzene-photoswitch-regulated RegX3 (Tris-thiourea transporter)               (AP-RegX3) Family 

Ajoene is a natural compound with enhanced antimycobacterial and antibiofilm properties mediated by efflux pump modulation and ROS generation against M. smegmatisSarangi et al. 2024 explored the potential of Ajoene, a naturally occurring garlic extract-derived compound, for potential TB treatment. Mycobacterium smegmatis was used to investigate Ajoene's efficiency. In vitro techniques like antimicrobial susceptibility, antibiofilm, EtBr accumulation assay, and ROS assay evaluated the potency of Ajoene and conventional TB drugs against Mycobacterium smegmatis. An in-silico study also investigated the interaction between Ajoene and quorum-sensing proteins, specifically RegX3, MSMEG_5244, and MSMEG_3944, which are involved in biofilm formation and sliding activity. Ajoene exhibited significant antibacterial activity by inhibiting growth and showing bactericidal effects. It also showed additive interactions with common antibiotics such as Isoniazid and Rifampicin. Furthermore, Ajoene demonstrated a comparative interaction with commonly used antibiotics, such as Isoniazid and Rifampicin, and reduced M. smegmatis motility, both alone and in combination with these antibiotics. In silico analysis shows that Ajoene exhibited a higher binding affinity with regX3, a protein orthologous to the regX3 gene in Mtb. Ajoene also demonstrated consistent antibiofilm effects, particularly when combined synergistically with Isoniazid and/or Rifampicin. Mechanistic investigations demonstrated Ajoene's potential to inhibit efflux pumps and promote ROS generation in bacteria, suggesting a potential direct killing mechanism (Sarangi et al. 2024).  Transporters 1 and 2 (see Sarangi et al. 2024) were synthesized in one step by reacting previously reported tris(2-isothiocyanatoethyl)amine with commercially available 4-aminoazobenzene and known 4-aminomethylazobenzene, respectively.

 

References associated with 1.D.283 family:

Sarangi, A., B.S. Das, I. Pahuja, S. Ojha, V. Singh, S. Giri, A. Bhaskar, and D. Bhattacharya. (2024). Ajoene: a natural compound with enhanced antimycobacterial and antibiofilm properties mediated by efflux pump modulation and ROS generation against M. Smegmatis. Arch. Microbiol. 206: 453. 39487375