期刊
PHARMACEUTICALS
卷 16, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/ph16020310
关键词
3D printing; catalyst compartmentation; polypropylene capsule; supported reagents; isatins; anticancer
This study demonstrates the application of 3D printing in chemical processes to obtain anticancer active pharmaceutical ingredients (APIs) using customized polypropylene permeable-capsule devices. The capsules are loaded with polymeric reagents, acting as catalysts or scavengers in chemical reactions. The reaction products, different series of diversely substituted isatins, showed potent antiproliferative activity against cancerous cervical and fibroblast cells.
The application of high throughput synthesis methodologies in the generation of active pharmaceutical ingredients (APIs) currently requires the use of automated and easily scalable systems, easy dispensing of supported reagents in solution phase organic synthesis (SPOS), and elimination of purification and extraction steps. The recyclability and recoverability of supported reagents and/or catalysts in a rapid and individualized manner is a challenge in the pharmaceutical industry. This objective can be achieved through a suitable compartmentalization of these pulverulent reagents in suitable devices for it. This work deals with the use of customized polypropylene permeable-capsule devices manufactured by 3D printing, using the fused deposition modeling (FDM) technique, adaptable to any type of flask or reactor. The capsules fabricated in this work were easily loaded in one step with polymeric reagents for use as scavengers of isocyanides in the work-up process of Ugi multicomponent reactions or as compartmentalized and reusable catalysts in copper-catalyzed cycloadditions (CuAAC) or Heck palladium catalyzed cross-coupling reactions (PCCCRs). The reaction products are different series of diversely substituted isatins, which were tested in cancerous cervical HeLa and murine 3T3 Balb fibroblast cells, obtaining potent antiproliferative activity. This work demonstrates the applicability of 3D printing in chemical processes to obtain anticancer APIs.
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