Abstract
Tellurium (Te) containing amino acids and their derivatives have the potential to participate in biological processes, which are currently being studied extensively to understand the function of Te in biological and pharmacological activities. Here, we are reporting the synthesis of two novel Te-containing unnatural amino acids; 1,3-Tellurazolidine-4-carboxylic acid [Te{CH2CH(COOH)NHCH2}] 5, and 4,4′-(1,2-Ditellurdiyl)bis(2-aminobutanoic acid), i.e., tellurohomocystine [TeCH2CH2CH(NH2)COOH]2 7, synthesized from tellurocystine, and l-methionine as precursors, respectively. These telluro-amino acids were thoroughly characterized by multinuclear (1H, 13C, 125Te) NMR spectroscopy, high-resolution ESI–mass spectrometry (ESI–MS), and elemental analysis. The telluro-amino acids 5 and 7 demonstrated good biocompatibility when in vitro cytotoxicity was analyzed on two fibroblast cell lines L929 and NIH/3T3. The treatment of telluro-amino acids 1,3-Tellurazolidine-4-carboxylic acid 5 and tellurohomocystine 7 on breast cancer cell line MCF-7 showed anticancer activity with IC50 values of 7.29 ± 0.27 µg/mL and 25.36 ± 0.12 µg/mL, respectively. The cell cycle distribution studies also revealed arrest at the sub-G1 phase suggesting telluro-amino acids to be apoptotic.
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Abbreviations
- ESI–MS:
-
Electrospray ionization–mass spectrometry
- DPBS:
-
Phosphate-buffered saline
- Te:
-
Tellurium
- Se:
-
Selenium
- Sec:
-
Selenocysteine
- Met:
-
Methionine
- NMR:
-
Nuclear magnetic resonance
- Phe:
-
Phenylalanine
- IC50:
-
Half maximal inhibitory concentration
- DMSO:
-
Dimethyl sulfoxide
- Te-APC:
-
Te-allophycocyanin
- Te-PC:
-
Te-phycocyanin
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Acknowledgements
Tripathi A. would like to acknowledge Prof (Retd.) Harkesh B. Singh and Bioorganic Chemistry Lab, Department of Chemistry, IIT Bombay, for providing the facility to synthesize telluro-amino acids 5 and 7. Khan A. and Srivastava R. would like to thank the cell culture and FACS facility of the Bioscience and Bioengineering department of IIT Bombay.
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TA produced the concept of present work. TA and KA designed the project under the guidance of SR. TA synthesized and characterized the telluro-amino acids 5 and 7. The biological studies were carried out by KA, with the supervision of SR. TA and KA wrote the original manuscript which was corrected, revised, and approved by all the authors for submission.
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Tripathi, A., Khan, A. & Srivastava, R. Synthesis and screening for anticancer activity of two novel telluro-amino acids: 1,3-Tellurazolidine-4-carboxylic acid and tellurohomocystine. Amino Acids 55, 1361–1370 (2023). https://doi.org/10.1007/s00726-023-03314-0
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DOI: https://doi.org/10.1007/s00726-023-03314-0