Design, synthesis, biochemical and in silico characterization of novel naphthalene-thiourea conjugates as potential and selective inhibitors of alkaline phosphatase

Abstract

Naphthalene ring is present in a number of FDA-approved, commercially available medications, including naphyrone, terbinafine, propranolol, naproxen, duloxetine, lasofoxetine, and bedaquiline. By reacting newly obtained 1-naphthoyl isothiocyanate with properly modified anilines, a library of ten novel naphthalene-thiourea conjugates ( 5a–5j ) were produced with good to exceptional yields and high purity. The newly synthesized compounds were observed for their potential to inhibit alkaline phosphatase (ALP) and scavenge free radicals. All of the investigated compounds displayed a more powerful inhibitory profile than the reference agent, KH 2 PO 4 particularly compound 5h and 5a exhibited strong inhibitory potential against ALP with IC 50 value of 0.365 ± 0.011 and 0.436 ± 0.057 µM respectively. In addition, Lineweaver–Burk plots revealed the non-competitive inhibition mode of the most powerful derivative i.e., 5h ( ki value 0.5 µM). To investigate the putative binding mode of selective inhibitor interactions, molecular docking was performed. It is recommended that future research will focus on developing selective alkaline phosphatase inhibitors by modifying the structure of the 5h derivative.

Naphthoyl benzhydrazine–decorated binuclear arene Ru(ii) complexes as anticancer agents targeting human breast cancer cells

“…In free ligands, the NMR signals attributed to the hydrazine (HN–NH) group were found in the downfield at 10.42–10.75 ppm. 11 These signals disappeared after coordination, confirming that the two ruthenium centers are bonded to the hydrazine nitrogen atoms in the ionized state (Fig. S10–S12†).…”

“…10 Furthermore, naphthalene, a potential cytotoxic moiety, was studied extensively as an antitumor, antimicrobial, antipsychotic, anti-inflammatory, antihypertensive, anti-neurodegenerative, and antidepressant agent. 11…”

Multisubstituted naphthalene synthesis from 4-hydroxy-2-pyrones through [4+2] cycloaddition with o-silylaryl triflates

“…Multisubstituted naphthalenes are a widely used class of compounds in various research areas such as pharmaceutical sciences, agrochemistry, and materials chemistry. 1 Despite the significance of highly functionalized naphthalenes, it is still challenging to prepare multisubstituted naphthalenes efficiently due to the problematic reactivity and selectivity control in various transformations such as electrophilic aromatic substitutions (Fig. 1A).…”