2. Academic Validation
  3. Benzofuran-Based Carboxylic Acids as Carbonic Anhydrase Inhibitors and Antiproliferative Agents against Breast Cancer

Benzofuran-Based Carboxylic Acids as Carbonic Anhydrase Inhibitors and Antiproliferative Agents against Breast Cancer

  • ACS Med Chem Lett. 2020 Mar 18;11(5):1022-1027. doi: 10.1021/acsmedchemlett.0c00094.
Wagdy M Eldehna 1 2,  Alessio Nocentini 3,  Zainab M Elsayed 2,  Tarfah Al-Warhi 4,  Nada Aljaeed 4,  Ohoud J Alotaibi 4,  Mohammad M Al-Sanea 5,  Hatem A Abdel-Aziz 6,  Claudiu T Supuran 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
  • 2 Scientific Research and Innovation Support Unit, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
  • 3 Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy.
  • 4 Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
  • 5 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia.
  • 6 Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt.
PMID: 32435420 DOI: 10.1021/acsmedchemlett.0c00094
Abstract

Pursuing our effort for developing effective inhibitors of the cancer-related hCA IX isoform, here we describe the synthesis of novel benzofuran-based carboxylic acid derivatives, featuring the benzoic (9a-f) or hippuric (11a,b) acid moieties linked to 2-methylbenzofuran or 5-bromobenzofuran tails via an ureido linker. The target carboxylic acids were evaluated for the potential inhibitory action against hCAs I, II, IX, and XII. Superiorly, benzofuran-containing carboxylic acid derivatives 9b, 9e, and 9f acted as submicromolar hCA IX inhibitors with KIs = 0.91, 0.79, and 0.56 μM, respectively, with selective inhibitory profile against the target hCA IX over the off-target isoforms hCA I and II (SIs: 2 to >63 and 4-47, respectively). Compounds 9b, 9e, and 9f were examined for their antiproliferative action against human breast Cancer (MCF-7 and MDA-MB-231) cell lines. In particular, 9e displayed promising antiproliferative (IC50 = 2.52 ± 0.39 μM), cell cycle disturbance, and pro-apoptotic actions in MDA-MB-231 cells.

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