Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential

Abstract

In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents.

Synthesis and biological activity of alkylthio and arylthio derivatives of tert-butylquinone

“…10 On the same bacterial strains, alkylamino, aralkylamino and amino acid derivatives of TBQ mostly showed stronger activity compared to TBQ. [12][13][14]…”

“…On the other hand, alkylamino and aralkylamino derivatives of TBQ generally had a higher activity than the parent compounds. 12,14…”

“…Avarol and avaron have shown great and diverse biological activity, such as antimicrobial, antiviral, antioxidant, and antitumor. [6][7][8][9][10] In our previous studies, the biological activity of avarol/avaron and their methoxy and methylamino derivatives 11 , alkylamino and aralkylamino derivatives, 12 amino acid derivatives, 13 and alkyl(aryl)thio derivatives 10 was examined. The yield of biologically active compounds originating from marine organisms is generally good, as is the case with avarol/avaron, but the problem is in the availability of marine organisms, so the solution could be to design specific synthetic compounds that are similar in structure and their derivatives in order to enhance activity and reduce potential side effects.…”