Exploring the Photodynamic Properties of Two Antiproliferative Benzodiazopyrrole Derivatives

• Main Authors: Concetta Imperatore, Mohammadhassan Valadan, Luciana Tartaglione, Marco Persico, Anna Ramunno, Marialuisa Menna, Marcello Casertano, Carmela Dell’Aversano, Manjot Singh, Maria Luisa d’Aulisio Garigliota, Francesco Bajardi, Elena Morelli, Caterina Fattorusso, Carlo Altucci, Michela Varra
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: International Journal of Molecular Sciences
• Subjects: photoswitchable azoheteroarene; diazo derivative; <i>cis</i>-<i>trans</i> conversion; fast uv spectroscopy; lc-hrms; conformational analysis; dft optimization
• Online Access: https://www.mdpi.com/1422-0067/21/4/1246

The identification of molecules whose biological activity can be properly modulated by light is a promising therapeutic approach aimed to improve drug selectivity and efficacy on the molecular target and to limit the side effects compared to traditional drugs. Recently, two photo-switchable diastereomeric benzodiazopyrrole derivatives <b>1RR</b> and <b>1RS</b> have been reported as microtubules targeting agents (MTAs) on human colorectal carcinoma p53 null cell line (HCT 116 p53-/-). Their IC₅₀ was enhanced upon Light Emitting Diode (LED) irradiation at 435&#8201;nm and was related to their <i>cis</i> form. Here we have investigated the photo-responsive behavior of the acid derivatives of <b>1RR</b> and <b>1RS</b>, namely, <i>d</i><b>1RR</b> and <i>d</i><b>1RS</b>, in phosphate buffer solutions at different pH. The comparison of the UV spectra, acquired before and after LED irradiation, indicated that the <i>trans</i><i>&#8594;</i><i>cis</i> conversion of <i>d</i><b>1RR</b> and <i>d</i><b>1RS</b> is affected by the degree of ionization. The apparent rate constants were calculated from the kinetic data by means of fast UV spectroscopy and the conformers of the putative ionic species present in solution (pH range: 5.7&#8722;8.0) were modelled. Taken together, our experimental and theoretical results suggest that the photo-conversions of <i>trans</i> <i>d</i><b>1RR</b>/<i>d</i><b>1RS</b> into the corresponding <i>cis</i> forms and the thermal decay of <i>cis</i> <i>d</i><b>1RR</b>/<i>d</i><b>1RS</b> are dependent on the presence of diazonium form of <i>d</i><b>1RR</b>/<i>d</i><b>1RS</b>. Finally, a photo-reaction was detected only for <i>d</i><b>1RR</b> after prolonged LED irradiation in acidic medium, and the resulting product was characterized by means of Liquid Chromatography coupled to High resolution Mass Spectrometry (LC-HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy.