Azobenzene-Tagged Photopeptides Exhibiting Excellent Selectivity and Light-Induced Cytotoxicity in MCF-7 Cells over HeLa and A549

Pradhan, S and Sarker, S and Thilagar, P (2024) Azobenzene-Tagged Photopeptides Exhibiting Excellent Selectivity and Light-Induced Cytotoxicity in MCF-7 Cells over HeLa and A549. In: Journal of Medicinal Chemistry, 67 (21). pp. 18794-18806.

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Abstract

The precise regulation of proteasome activity has become a focal point in current research, particularly its implications in cancer treatment. Bortezomib is used for treating multiple myeloma and is found to be ineffective against solid tumors. A spatiotemporal control over the proteasome is one of the solutions to resolve these issues using external stimuli, such as light. Thus, we designed and synthesized azobenzene-containing tripeptide vinyl sulfones 1, 2, 3, and 4, as the azobenzene moiety can impart E�Z isomerism upon exposure to UV light. Further, the hydrophobicity of these peptides was fine-tuned by systematically varying the size of hydrophobic amino acids at the P1, P2, and P3 positions. The light-induced Z isomers of these photopeptides showed excellent cellular potency in HeLa, MCF-7, and A549 cell lines. Photopeptide 4 with valine at the proximal position, phenylalanine at P2, and leucine at the P1 positions exhibited 19.3- and 6.6-fold cellular potency in MCF-7 and A549 cells, respectively. © 2024 American Chemical Society.

Item Type:	Journal Article
Publication:	Journal of Medicinal Chemistry
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to Journal of Medicinal Chemistry
Keywords:	2 (3,3 dimethylbutanamido) n methoxy n,4 dimethylpentanamide; 2 (tert butoxycarbonyl)amino 3 4 (phenyldiazenyl)phenylpropanoic acid; 3 (3,5 dimethylphenyl)diazenyl n 1 4 methyl 1 (5 methyl 1 (methylsulfonyl)hex 1 en 3 ylmino 1 oxopentan 2 ylamino 1 oxo 3 phenylpropan 2 ylbenzamide; 3 (3,5 dimethylphenyl)diazenyl n 3 methyl 1 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 yl)amino 1 oxo 3 phenylpropan 2 ylamino 1 oxobutan 2 ylbenzamide; 3 (3,5 dimethylphenyl)diazenyl n 4 methyl 1 4 methyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 yl]amino] 1 oxopentan 2 yl]amino] 1 oxopentan 2 yl]benzamide; 6 5 methyl 1 (methylsulfonyl)hex 1 en 3 amine; azobenzene derivative; cytotoxic agent; methyl 4 (phenyldiazenyl)benzoylphenylalanine; n 1 3 methyl 1 (3a,5,5 trimethylhexahydro 4,6 methanobenzod]1,3,2dioxaborol 2 yl)butylamino 1 oxo 3 phenylpropan 2 yl 4 (phenyldiazenyl)benzamide; n 3 (1h indol 3 yl) 1 (4-methyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxopentan 2 ylamino 1 oxopropan 2 yl 3 ((3,5 dimethylphenyldiazenylbenzamide; proteasome; proteasome inhibitor; sulfone derivative; tert butyl (4 methyl 1 oxopentan 2 yl)carbamate; tert butyl 1 3 methyl 1 ( 3a,5,5 trimethylhexahydro 4,6 methanobenzod1,3,2dioxaborol 2 yl)butylamino 1 oxo 3 4 (phenyldiazenyl)phenylpropan 2 ycarbamate; tert butyl 1 4 methyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxopentan 2 ylamino 1 oxo 3 phenylpropan 2 ylcarbamate; tert butyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxo 3 phenylpropan 2 ylcarbamate; tert butyl 3 (1h indol 3 yl) 1 4 methyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxopentan 2 ylamino 1 oxopropan 2 ylcarbamate; tert butyl 3 methyl 1 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxo 3 phenylpropan 2 ylamino 1 oxobutan 2 ylcarbamate; tert butyl 4 methyl 1 4 methyl 1 5 methyl (methylsulfonyl)hex 1 en 3 ylamino 1 oxopentan 2 ylamino 1 oxopentan 2 ylcarbamate; tert butyl 4 methyl 1 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylamino 1 oxopentan 2 ylcarbamate; tert butyl 5 methyl 1 (methylsulfonyl)hex 1 en 3 ylcarbamate; tripeptide derivative; unclassified drug; vinyl derivative; 3 methyl 1 3 phenyl 2 4 (phenyldiazenyl)benzamidopropanamidobutylboronic acid; 4 (phenyldiazenyl)benzoylphenylalanine; antineoplastic agent; azo compound; azobenzene; oligopeptide; peptide, A-549 cell line; antineoplastic activity; apoptosis; Article; binding site; cell viability assay; conformation; controlled study; cytotoxicity; drug design; drug selectivity; enzyme inhibition; female; HeLa cell line; human; human cell; hydrophobicity; IC50; in vitro study; isomerism; MCF-7 cell line; molecular docking; reversed phase high performance liquid chromatography; ultraviolet radiation; A-549 cell line; chemistry; drug screening; HeLa cell line; MCF-7 cell line; structure activity relation; synthesis, A549 Cells; Antineoplastic Agents; Azo Compounds; Drug Screening Assays, Antitumor; HeLa Cells; Humans; MCF-7 Cells; Oligopeptides; Peptides; Structure-Activity Relationship; Ultraviolet Rays
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	12 Dec 2024 18:47
Last Modified:	12 Dec 2024 18:47
URI:	http://eprints.iisc.ac.in/id/eprint/87024

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