Optimization of gram-scale synthesis of triazolylaminoacilpenicillins and analogs. In vivo antitumoral activity against murine mammary adenocarcinoma

BOGGIÁN, D; DEL GIUDICE ANTONELA; ROZADOS V; DELPICCOLO, C.; GIOLITO MV; M. J. RICO; CORNIER P; MATA E; OG SCHAROVSKY

Rosario

Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticas ? RICIFA 2016; 2016

Ricifa

We have previously synthesized a library of triazolylaminoacyl(peptidyl)penicillins and analogs. An efficient and versatile solid-phase methodology was used for their quick and easy synthesis.1 Several compounds of this library have shown a remarkable in vitro antiproliferative activity.2 Hence, in order to be able to develop in vivo studies of the active compounds, our aim was to develop a new synthesis process for obtaining triazolylaminoacyl(peptidyl)penicillins and analogs in grams scale. Homogeneous chemistry is efficient and significantly reduces the cost of the process. So, we optimized the synthetic route for obtaining the desired compounds in 5 steps, with good overall yields. After optimization, in vivo studies were carried out. Inbred CBi female mice, bearing M-406 mammary adenocarcinoma were administered i.p. with compound 21 (60 mg/kg body weight), 3 times/week, during two weeks. Control mice did not received treatment. Tumors were measured twice/week. A significant inhibition of tumor size was observed on day 12, compared to controls (P