Malays. J. Anal. Sci. Volume 29 Number 4 (2025): 1489

 

Research Article

 

4-amidobenzhydryl analogue as stable acetoxychavicol acetate (ACA): Synthesis, characterisation and cytotoxic activity against human myeloid leukaemia cell lines (KASUMI-1)

 

Mohamad Nurul Azmi1*, Cheong Siong Tan1, Siti Nurshahira Mohd Radzuan1, Mahdi Babai1,2, Nozlena Abdul  Samad3, Julia Joseph3,4, and Pinus Jumaryatno5

 

1Natural Products and Organic Synthesis Laboratory (NPSO), School of Chemical Sciences, Universiti Sains Malaysia,         11800 Minden, Penang, Malaysia.

2Department of Chemistry, Nigerian Army University Biu, Borno State, 1500, Nigeria

3Department of Toxicology, Advance Medical and Dental Institute, Sains@Bertam, 13200 Kepala Batas, Penang, Malaysia

4Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah,88400, Kota Kinabalu, Sabah, Malaysia

5Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Indonesia, Yogyakarta 55584,                Indonesia

 

*Corresponding author: mnazmi@usm.my

 

Received: 28 February 2025; Revised: 17 June 2025; Accepted: 18 June 2025; Published: 22 August 2025

 

Abstract

A series of 4-amidobenzhydryl-type analogues, designed as mimics of the stable compound 1′-acetoxychavicol acetate (ACA), were successfully synthesised by acylation reaction of (4-aminophenyl)(phenyl)methanol with various acyl chlorides. All the synthesised analogues were fully characterised by comprehensive spectroscopic techniques. The cytotoxic activity of these analogues was evaluated using the MTT assay against the human myeloid leukemia cell line Kasumi-1. The structure-activity relationship (SAR) analysis was conducted to examine the impact of different functional groups on the cytotoxic properties of the compounds. Compound 3a exhibit the highest cytotoxic activity with IC50 values of 247.35 µM (24h), 106.01 µM (48h) and 98.94 µM (72h). SAR analysis indicated that aliphatic substitutions at the carboxamide and ester positions enhanced cytotoxic activity, while phenyl and cyclohexyl substitutions resulted in decreased activity. These results indicate that 4-amidobenzhydryl analogues, in particular compound 3a, are promising anticancer agents, with compound 3a emerging as a lead candidate for further development.

 

Keywords: 4-amidobenzhydryl-type analogues, 1′-acetoxychavicol acetate, cytotoxic, MTT assay, human myeloid leukemia

 

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