Design, Synthesis and Cytotoxic Activity Evaluation of Newly Synthesized Amides-Based TMP Moiety as Potential Anticancer Agents over HepG2 Cells

Tarfah Al-Warhi; Adil Aldhahrani; Fayez Althobaiti; Eman Fayad; Ola A. Abu Ali; Sarah Albogami; Ali H. Abu Almaaty; Amgad I. M. Khedr; Syed Nasir Abbas Bukhari; Islam Zaki

doi:10.3390/molecules27123960

Molecules (Jun 2022)

Design, Synthesis and Cytotoxic Activity Evaluation of Newly Synthesized Amides-Based TMP Moiety as Potential Anticancer Agents over HepG2 Cells

Tarfah Al-Warhi,
Adil Aldhahrani,
Fayez Althobaiti,
Eman Fayad,
Ola A. Abu Ali,
Sarah Albogami,
Ali H. Abu Almaaty,
Amgad I. M. Khedr,
Syed Nasir Abbas Bukhari,
Islam Zaki

Affiliations

Tarfah Al-Warhi: Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Adil Aldhahrani: Clinical Laboratory Sciences Department, Turabah University Faculty, Taif University, Taif 21995, Saudi Arabia
Fayez Althobaiti: Department of Biotechnology, Faculty of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Eman Fayad: Department of Biotechnology, Faculty of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Ola A. Abu Ali: Department of Chemistry, College of Science, Taif University, P.O. Box 11099 Taif 21944, Saudi Arabia
Sarah Albogami: Department of Biotechnology, Faculty of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Ali H. Abu Almaaty: Zoology Department, Faculty of Science, Port Said University, Port Said 42526, Egypt
Amgad I. M. Khedr: Department of Pharmacognosy, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt
Syed Nasir Abbas Bukhari: Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia
Islam Zaki: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt

DOI: https://doi.org/10.3390/molecules27123960
Journal volume & issue: Vol. 27, no. 12
p. 3960

Abstract

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A novel series of amides based TMP moiety was designed, synthesized and evaluated for their antiproliferative as well as enzyme inhibition activity. Compounds 6a and 6b showed remarkable cytotoxic activity against HepG2 cells with IC50 values 0.65 and 0.92 μM, respectively compared with SAHA and CA-4 as reference compounds. In addition, compound 6a demonstrated good HDAC-tubulin dual inhibition activity as it showed better HDAC activity as well as anti-tubulin activity. Moreover, compound 6a exhibited G2/M phase arrest and pre-G1 apoptosis as demonstrated by cell cycle analysis and Annexin V assays. Further apoptosis studies demonstrated that compound 6a boosted the level of caspase 3/7. Caspase 3/7 activation and apoptosis induction were evidenced by decrease in mitochondrial permeability suggesting that activation of caspase 3/7 may occur via mitochondrial apoptotic pathway.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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