Synthesis, in silico ADME, molecular docking and in vitro cytotoxicity evaluation of stilbene linked 1,2,3-triazoles

Abstract

Series of (E)-1-benzyl-4-((4-styrylphenoxy)methyl)-1H-1,2,3-triazoles 7a-x were obtained by Wittig reaction between 4-((1-benzyl-1H-1,2,3-triazol-4-yl)methoxy)benzaldehydes 5a-d and benzyl triphenylphosphonium halides 6a-f in benzene. The structures of the synthesized compounds were confirmed by FTIR, NMR ( 1 H and 13 C NMR) spectroscopy, and mass spectrometry. All synthesized compounds were screened for their cytotoxic activity against human cancer cell lines including pancreatic carcinoma, colorectal carcinoma, lung carcinoma, and leukemias such as acute lymphoblastic, chronic myeloid, and non-Hodgkinson lymphoma cell lines. In vitro cytotoxicity data showed that compounds 7c, 7e, 7h, 7j, 7k, 7r, and 7w were moderately cytotoxic (11.6-19.3 μM) against the selected cancer cell lines. These cytotoxicity findings were supported using molecular docking studies of the compounds against 1TUB receptor. The drug-likeness properties of the compounds evaluated by in silico ADME analyses. Resveratrol linked 1,2,3-triazoles were more sensitive towards human carcinoma cell lines but least sensitive towards leukemia and lymphoma cell lines.

Study of the Lipophilicity and ADMET Parameters of New Anticancer Diquinothiazines with Pharmacophore Substituents

“…It is known that lipophilicity is one of the most frequently studied physicochemical parameters of new substances that are drug candidates [ 19 , 40 ]. It is most often defined to support quantitative structure–activity relationships (QSARs), including absorption, distribution in tissues, and drug transport across the biological barrier [ 41 , 42 , 43 ].…”

Medicinal chemistry perspective on the structure–activity relationship of stilbene derivatives

“…Das et al 81 synthesized and tested stilbene-linked 1,2,3-triazoles against six cell lines. All the synthesized compounds showed lower cytotoxicity activity than docetaxel and staurosporine against the HCT-116, Capan-1, K-562, DND-41, Z-138, and NCI-H460 cell lines.…”

Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

“…1,2,3-Triazole is a well-known scaffold with substantial biologicalactivities. In fact, 1,2,3-triazole derivatives have been reported as anticancer (Atulya et al, 2016, Chen et al,2008, Narsimha et al, 2016, Carroux et al, 2013, Duan et al, 2013, Yan et al,2010, Sztankeet al, 2008, cytotoxic (Das et al, 2021), antioxidant (Mady et al, 2014), anti-HIV (Velázquez et al, 1998, Johns etal., 2009, anti-tubercular (Kumar et al, 2014, Yempala et al, 2014, Patpi et al, 2012, antimicrobial (Hussain et al, 2019, Behbehani et al,2011, Holla et al, 2005, Chen et al,2000,antifungal (Sheehan et al,1999), antiinflammatory (Hafez et al, 2008, Rao etal., 2014, antimalarial (Gujjar et al, 2009), and anticonvulsant (Ulloora et al, 2013, Erol et al, 1995 agents. Apart from being a versatile synthon, the triazole moiety is used as bioisostere to modify biological and physicochemical properties of a lead in drug discovery process (Bonandi et al, 2017).…”