Exploring the Photodynamic Properties of Two Antiproliferative Benzodiazopyrrole Derivatives

International Journal of Molecular Sciences

Michela Varra¹  Carmela Dell’Aversano¹  Marcello Casertano¹  Luciana Tartaglione¹  Concetta Imperatore¹  Caterina Fattorusso¹  Marco Persico¹  Elena Morelli¹  Marialuisa Menna¹  Anna Ramunno²  MariaLuisa d’Aulisio Garigliota²  Manjot Singh³  Carlo Altucci³  Francesco Bajardi³  Mohammadhassan Valadan³ 

[1] Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy;Department of Pharmacy/DIFARMA, University of Salerno, 84084 Fisciano, Salerno, Italy;Department of Physics “Ettore Pancini”, University of Naples Federico II, 80126 Naples, Italy;

关键词: photoswitchable azoheteroarene;    diazo derivative;    cis-trans conversion;    fast uv spectroscopy;    lc-hrms;    conformational analysis;    dft optimization;   

DOI  :  10.3390/ijms21041246

来源: DOAJ

【 摘 要 】

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 1RR and 1RS 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 nm and was related to their cis form. Here we have investigated the photo-responsive behavior of the acid derivatives of 1RR and 1RS, namely, d1RR and d1RS, in phosphate buffer solutions at different pH. The comparison of the UV spectra, acquired before and after LED irradiation, indicated that the trans→cis conversion of d1RR and d1RS 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: 5.7−8.0) were modelled. Taken together, our experimental and theoretical results suggest that the photo-conversions of trans d1RR/d1RS into the corresponding cis forms and the thermal decay of cis d1RR/d1RS are dependent on the presence of diazonium form of d1RR/d1RS. Finally, a photo-reaction was detected only for d1RR 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.

【 授权许可】

Unknown