Searching for new derivatives of neocryptolepine: Synthesis, antiproliferative, antimicrobial and antifungal activities

• Amino acid and dipeptide derivatives of neocryptolepine were synthesized.
• New derivatives displayed high antiproliferative activity in vitro.
• Some of them possessed antimicrobial activity against Gram-positive bacteria.
• The tested derivatives to be potent agents against Candida albicans in vitro biofilms.
• Lower doses for activity against biofilms than needed against free fungal cells.

A series of novel amino acid and dipeptide derivatives of neocryptolepine were synthesized and tested for their antimicrobial, antifungal and antiproliferative activity in vitro against cancer cell lines (KB, A549, MCF-7, LoVo) and normal mice fibroblast cells (BALB/3T3). Biological evaluation revealed that almost all of the new compounds displayed high antiproliferative activity against the tested cells and moderate to potent antibacterial activities. Interestingly, these compounds were active against Candida albicans biofilms at doses significantly lower than those required against free-floating planktonic fungal cells. The most promising compounds are derivatives with glycine and l-proline as a substituent both at 2 and at 9 position of 5H-indolo[2,3-b]quinoline. In general, these new compounds (2a, 3a, 6a and 7a) showed the highest dual action against cancer lines and infectious pathogenic microbes in vitro.

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