American Chemical Society
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Design, Microwave-Assisted Synthesis, Antimicrobial and Anticancer Evaluation, and In Silico Studies of Some 2‑Naphthamide Derivatives as DHFR and VEGFR‑2 Inhibitors

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journal contribution
posted on 2022-09-15, 16:31 authored by Em Canh Pham, Tuyen Ngoc Truong
Naphthamide is a common structural framework with diverse pharmacological activities. Ten novel 2-naphthamide derivatives have been designed, synthesized, and evaluated for their in vitro antibacterial, antifungal, and anticancer activities. The title compounds were synthesized from dimethoxybenzaldehyde derivatives through a four-step microwave-assisted synthesis process. The structures were confirmed by 1H NMR, 13C NMR, and MS spectra. Compound 8b showed good antibacterial activity against Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA, and MRSA with MIC values of 16, 16, 16, 8, and 16 μg/mL, respectively, compared to ciprofloxacin (MIC = 8–16 μg/mL). Compounds 5b (IC50 = 3.59–8.38 μM) and 8b (IC50 = 2.97–7.12 μM) exhibited good cytotoxic activity against C26, HepG2, and MCF7 cancer cell lines as compared to paclitaxel (IC50 = 2.85–5.75 μM). Moreover, compounds 5b and 8b exhibited better anticancer activity than PTX against the C26 cell line. In particular, compound 8b showed potent in vitro VEGFR-2 inhibitory activity with the IC50 value of 0.384 μM compared with sorafenib (IC50 = 0.069 μM). Therefore, compound 8b is the most potent compound for anticancer activity as indicated by in vitro cell line inhibition, in silico ADMET, molecular docking, and in vitro VEGFR-2 inhibition studies.