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Cu-promoted synthesis of triclosan-Mannich and Glaser adducts: anti-mycobacterial evaluation with in silico validations.

null ShekharMatthéo AlcarazAmit AnandRajni Kant SharmaLaurent KremerVipan Kumar
Published in: Future medicinal chemistry (2024)
Aim:  The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.1 million reported in 2020. The incidence rate of TB showed 3.6% rise from 2020 to 2021. Results/methodology: This manuscript discloses Cu-promoted single pot A 3 -coupling between triclosan (TCS)-based alkyne, formaldehyde and secondary amines to yield TCS-based Mannich adducts. Additionally, the coupling of TCS-alkynes in the presence of Cu(OAc) 2 afforded the corresponding homodimers. Among tested compounds, the most potent one in the series 11 exhibited fourfold higher potency than rifabutin against drug-resistant Mycobacterium abscessus . The selectivity index was also substantially improved, being 26 (day 1) and 15 (day 3), which is four-times better than TCS.
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