Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM-15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC50 values of 0.23 and 1.29 µM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC50 values of 14.0, 13.7 and 13.0µM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM-15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention.
A facile, efficient, and gram‐scale method for the conversion of para‐anisic acid into 3,4,5‐triiodoanisole through a one‐pot C–H iodination/ipso‐iododecarboxylation reaction was investigated. Commercially available benzoic acid was used, which allowed the reaction to be performed on a multigram scale in good yield. This report discloses a practical method for the one‐pot synthesis of hitherto unknown 3,4,5‐triiodoanisole that is catalytic, scalable, efficient, and easy to work up and purify. Potential application of the target compound as a precursor for novel site‐selective metal–iodine exchange and Suzuki–Miyaura cross‐coupling reactions were also explored. 3,4,5‐Trisubstituted anisole derivatives were provided in a highly regioselective fashion; these compounds are useful building blocks in synthesis and indeed are hard to prepare by any other means.
A series of iodinated benzoboroxoles was designed and synthesized by using a successive metal–iodine exchange reaction of 3,4,5‐triiodoanisole. The reactivity and regioselectivity of the metal‐iodine exchange are remarkably controlled and provide the iodinated products in good yields. The synthesized iodobenzoboroxoles were screened for in vitro antimicrobial activity against two Gram‐positive strains of bacteria, Micrococcus luteus (ATCC 9341) and Bacillus cereus (ATCC 11778), and two Gram‐negative strains, Escherichia coli (ATCC 25922) and Serratia marcescens (ATCC 27117), by using a well‐diffusion assay and dilution methods. The in vitro antimicrobial evaluation indicated that 4‐iodo‐6‐methoxybenzo[c][1,2]oxaborol‐1(3H)‐ol (compound 24) possesses the most‐potent antibacterial activity against Gram‐positive strains with a minimum inhibitory concentration (MIC) of 0.016 and 0.013 mg/mL for Micrococcus luteus and Bacillus cereus, respectively. This report discloses a two‐step protocol for the synthesis of hitherto unknown 4‐iodobenzoboroxole and 7‐iodobenzoboroxole derivatives that is efficient, general in scope and scalable.
An efficient and versatile synthesis of 2,6-diiodobenzaldehydes via highly regioselective metal–iodine exchange (MIE) of 5-substituted 1,2,3-triiodobenzenes is reported. The nature of substituents (R) on the phenyl has a large influence on the reactivity of reaction but not on the regioselectivity. The regioselectivity of the MIE can be controlled by the use of ethyl formate as a formylating agent providing only the internal benzaldehyde derivatives in excellent site-selectivity. The best reactivity and the highest isolated yields were furnished with products bearing electron-rich substituents. Several chemical transformations of the target compound as a valuable precursor in synthesis were also demonstrated providing the desired derivatives in good isolated yields. This report discloses a protocol for the synthesis of 2,6-diiodobenzaldehyde derivatives that is scalable, general in scope, and indeed difficult to be made by other means.
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