Synthesis of a novel series of 2,3,4-trisubstituted oxazolidines designed by isosteric replacement or rigidification of the structure and cytotoxic evaluation

Abstract

Rigidification of the structure of 2,3,4-trisubstituted oxazolidines enhances the activity against LNCaP cells without affecting normal cell proliferation.

Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box

“…The rationale behind compound synthesis was based on previous observations regarding substituent groups. Interestingly, substituent groups at 3 or 4-position were found to be paramount for compound activity, and while ortho -substituted compounds were found to be inactive in targeting cancer cells S isomer were the most potent, often being 10 times more active than their enantiomers, By exploiting these characteristics and by exploiting the importance of the oxymethylene spacer between benzene and oxazolidine rings the synthetized compounds were found to exhibited in general high cytotoxic activities with low IC 50 concentrations against a cancer cell line panel composed of, HL60, JURKAT (peripheral blood), MDA-MB-231 (mammary gland) and LNCaP (prostate) [51]. More significantly, the derivative ( S )-tert-butyl 2,2-dimethyl-4-(1-(4-nitrophenyl)vinyl)oxazolidine-3-carboxylate ( 23 ) (Figure 13) exhibited a cytotoxic activity similar to the remaining derivatives, however, with exception for LNCaP cell line for which it presented high affinity with a IC 50 value in the micromolar range (11 μM).…”

“…Chemical structure representation of 2,3,4-trisubstituted oxazolidines core scaffold ( 22 ) and oxazolidine derivative, ( S )-tert-butyl 2,2-dimethyl-4-(1-(4-nitrophenyl)vinyl)oxazolidine-3-carboxylate ( 23 ) with proven anticancer activity against HL60, JURKAT, MDA-MB-231 and LNCaP [51]. …”

An Efficient Synthesis for Some New Heterocyclic Compound‐fused Oxindole Derivatives

“…Imidazolidine and oxazolidine derivatives are important class of molecules because this fragment is a key moiety in numerous biologically active and drug molecules . These heterocycles compounds were reported as cytotoxic evaluation against cancer cell lines , anti‐Trypanosoma cruzi agents anti‐inflammatory , analgesic , α ‐adrenergic receptor agonist , antimicrobial , antiparasitic , antitubercular , antibacterial , and anticonvulsant activities . Several methods have been reported for the synthesis of imidazolidine and oxazolidine .…”