2. Academic Validation
  3. Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues

  • ACS Omega. 2023 Oct 9;8(41):38394-38405. doi: 10.1021/acsomega.3c05051.
Eman Fayad 1,  Sarah Awwadh Altalhi 1,  Matokah M Abualnaja 2,  Abdulmohsen H Alrohaimi 3,  Fahmy G Elsaid 4,  Ali H Abu Almaaty 5,  Rasha Mohammed Saleem 6,  Mohammed A Bazuhair 7,  Ali Hassan Ahmed Maghrabi 8,  Botros Y Beshay 9,  Islam Zaki 10
Affiliations

Affiliations

  • 1 Department of Biotechnology, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
  • 2 Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Al Mukarrama 24230, Saudi Arabia.
  • 3 Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia.
  • 4 Biology Department, College of Science, King Khalid University, P.O.Box 960, Asir, Abha 61421, Saudi Arabia.
  • 5 Zoology Department, Faculty of Science Port Said University, Port Said 42526, Egypt.
  • 6 Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha 65431, Saudi Arabia.
  • 7 Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 8 Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah 24381, Saudi Arabia.
  • 9 Pharmaceutical Sciences (Pharmaceutical Chemistry) Department, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria 21913, Egypt.
  • 10 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Port Said University, Port Said 42526, Egypt.
PMID: 37867686 DOI: 10.1021/acsomega.3c05051
Abstract

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 μM, as compared to CA-4 (IC50 = 1.27 ± 09 μM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against β-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed LIGHT on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

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