In vitro and in silico perspectives to explain anticancer activity of a novel syringic acid analog ((4-(1H-1, 3-benzodiazol-2-yl)-2, 6-dimethoxy phenol)) through apoptosis activation and NFkB inhibition in K562 leukemia cells

Cheemanapalli, S and Palaniappan, C and Mahesh, Y and Iyyappan, Y and Yarrappagaari, S and Kanagaraj, S (2022) In vitro and in silico perspectives to explain anticancer activity of a novel syringic acid analog ((4-(1H-1, 3-benzodiazol-2-yl)-2, 6-dimethoxy phenol)) through apoptosis activation and NFkB inhibition in K562 leukemia cells. In: Computers in Biology and Medicine, 152 .

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Abstract

Syringic acid (SA) is an active carcinogenesis inhibitor; however, the low bioavailability and unstable functional groups hinder its activity. Here, a chemically synthesized novel SA analog (SA10) is evaluated for its anticancer activity using in-vitro and in-silico studies. K562 cell line study revealed that SA10 had shown a higher rate of inhibition (IC50 = 50.40 μg/mL) than its parental compound, SA (IC50 = 96.92 μg/mL), at 50 μM concentration. The inhibition ratio was also been evaluated by checking the expression level of NFkB and Bcl-2 and showing that SA10 has two-fold increase in the inhibitory mechanism than SA. This result demonstrates that SA10 acts as an NFkB inhibitor and an apoptosis inducer. Further, molecular docking and simulation have been performed to get insights into the possible inhibitory mechanism of SA and SA10 on NFkB at the atomistic level. The molecular docking results exemplify that both SA and SA10 bind to the active site of NFkB, thereby interfering with the association between DNA and NFkB. SA10 exhibits a more robust binding affinity than SA and is firmly docked well into the interior of the NFkB, as confirmed by MM-PBSA calculations. In a nutshell, the Benzimidazole scaffold containing SA10 has shown more NFkB inhibitory activity in K562 cells than SA, which could be helpful as an ideal therapeutic NFkB inhibitor for treating cancers.

Item Type:	Journal Article
Publication:	Computers in Biology and Medicine
Publisher:	Elsevier Ltd
Additional Information:	The copyright for this article belongs to Elsevier Ltd.
Keywords:	Syringic acidCarcinogenesisK562 cellsNFkBDockingSimulation
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited:	13 Jan 2023 09:51
Last Modified:	13 Jan 2023 09:51
URI:	https://eprints.iisc.ac.in/id/eprint/79125

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