2. Academic Validation
  3. Microwave-assisted synthesis of tubulin assembly inhibitors as anticancer agents by aryl ring reversal and conjunctive approach

Microwave-assisted synthesis of tubulin assembly inhibitors as anticancer agents by aryl ring reversal and conjunctive approach

  • RSC Med Chem. 2025 Jul 2;16(10):4845-4858. doi: 10.1039/d5md00406c.
Domiziana Masci 1 2,  Michela Puxeddu 3,  Claudia Colla 3,  Antonio Coluccia 3,  Martina Santelli 1,  Pietro Sciò 3,  Elena Mariotto 4 5,  Giampietro Viola 4 5,  Ernest Hamel 6,  Rosa Lerose 7,  Carmela Mazzoccoli 7,  Romano Silvestri 3,  Giuseppe La Regina 3
Affiliations

Affiliations

  • 1 Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Catholic University of the Sacred Heart Largo Francesco Vito 1 00168 Rome Italy.
  • 2 Policlinico Universitario A. Gemelli Foundation-IRCCS 00168 Rome Italy.
  • 3 Laboratory affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome Piazzale Aldo Moro 5 00185 Rome Italy romano.silvestri@uniroma1.it.
  • 4 Department of Woman's and Child's Health, University of Padua, Hemato-oncology Lab Via Giustiniani 3 35128 Padua Italy.
  • 5 Istituto di Ricerca Pediatrica Città della Speranza - IRP Corso Stati Uniti 4-35127 Padua Italy.
  • 6 Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health Frederick Maryland 21702 USA.
  • 7 Hospital Pharmacy, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB) 85028 Rionero in Vulture Italy.
PMID: 40741052 DOI: 10.1039/d5md00406c
Abstract

Microwave-assisted synthesis of new pyrrole and indole derivatives as tubulin assembly inhibitors was performed with remarkably improved yields and short reaction times. In designing the new inhibitors, aryl ring reversal and conjunctive approach notions were applied. (4-(4-Methoxyphenyl)-1-(pyridin-2-yl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl) methanone (4) inhibited [3H] colchicine binding by 78% and MCF-7 breast Cancer cell growth with an IC50 of 9.6 nM. Compound 4 also inhibited the growth of HCT116, BX-PC3 and Jurkat Cancer cells with IC50 values of 18, 17 and 41 nM, respectively, and altered the morphology of treated spheroids in both the BX-PC3 and HCT116 cell lines.

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