Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: a structure–activity relationship study

Abstract

In the course of structure-activity relationship studies and to explore the antiproliferative effect associated with the hydantoin framework, diversely substituted several diazaspiro hydantoins were synthesized. Variation in the functional group at N-terminal of the hydantoin ring and coupling of different substituted aromatic acids in 4-aminocyclohexanone ring led to three sets of compounds. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (NDF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, some compounds exhibited interesting growth inhibitory effects against all four cell lines. From the SAR studies, it reveals that, the substitution at N-terminal in hydantoin ring plays key role in the antiproliferative activity.

Synthesis and in vitro cytotoxic evaluation of novel diazaspiro bicyclo hydantoin derivatives in human leukemia cells: A SAR study

“…Recently, we have investigated the synthesis of bioactive heterocycles and evaluation of their antiproliferative activity against different carcinoma cell lines [15,16]. Our investigation on the synthesis of different substituted diazaspiro hydantoin derivatives and evaluation of their antitumor activities unraveled that the fluorine substituted hydantoin analogs possessed potent antitumor activity [16].…”

“…Our investigation on the synthesis of different substituted diazaspiro hydantoin derivatives and evaluation of their antitumor activities unraveled that the fluorine substituted hydantoin analogs possessed potent antitumor activity [16]. Inspired by these results, as part of our strategy towards the synthesis and biological evaluation of fluorinated and other bioactive heterocycles [17][18][19], we have designed a new series of more constrained derivatives of diazaspiro bicyclo hydantoin bearing fluorine and chlorine.…”

“…Inspired by these results, as part of our strategy towards the synthesis and biological evaluation of fluorinated and other bioactive heterocycles [17][18][19], we have designed a new series of more constrained derivatives of diazaspiro bicyclo hydantoin bearing fluorine and chlorine. The design of substituents at N−3 and N−8 position was based on previous results [16] and the choice of substituents in position N−3 was limited to alkene, ester and ether group. The purpose of the present study is to examine the effects of more constrained hydantoin derivatives having exocyclic double bond, ester and ether group against cell proliferation in leukemia cells, K562 and CEM.…”

New platinum(II) complexes of cycloalkanespiro-5-(2-thiohydantoins). Synthesis and quantum chemical investigation

“…as antiepileptic drugs. 18,19 Antiproliferative effects, 20,21 inhibition of aldosoreductase 22 and potential application for treatment of HIV-1 infections 23,24 were also described. Recently, we reported the synthesis of various thioanalogues of cycloalkanespiro-5-hydantoins.…”

Study on the Synthesis, Characterization and Bioactivities of 3-Methyl-9’-fluorenespiro-5-hydantoin

“…In the course of structure-activity relationship (SAR) studies and to explore the antiproliferative effect associated with the hydantoin framework, several diversely substituted diazaspiro hydantoins were synthesized. 48 Variation in the functional group at N-terminal of the hydan-toin ring and coupling of different substituted aromatic acids in 4-aminocyclohexanone ring led to three sets of compounds. The antiproliferative effect of the compounds was evaluated in vitro using the MTT test against one normal cell line (NDF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, some compounds exhibited interesting growth inhibitory effects against all four cell lines.…”