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Pharmaceutical Chemistry Journal, Vol. 54, No. 9, December, 2020 (Russian Original Vol. 54, No. 9, September, 2020)

SYNTHESIS AND IN VITRO STUDIES OF O-ALKYLAMINOETHYLATED DERIVATIVES OF 3E-HYDROXIMINOCHOLESTENE AS POTENT AND SELECTIVE ANTILEUKEMIC AGENTS Amruta Suryan1 and Ranju Bansal1,* Original article submitted November 27, 2018. New O-alkylaminoethylated derivatives of 3-hydroximinocholestene were synthesised and studied for in vitro cytotoxic effects. The obtained oily oxime ethers were solidified by preparing their oxalate salts. The steroidal compounds were screened against 60 human cancer cell lines at 10 mM. The study indicated that the compounds display selective cytotoxicity against leukemia cell lines. Dimethylamine (7a) and pyrrolidine (7d) derived O-alkylated steroidal oxalates displayed percent growth inhibition of 73.36 % and 69.97 %, respectively, against CCRF-CEM leukemia cancer cell line. Partition coefficient values of the new steroids were also estimated to study the correlation of lipophilicity with the biological activity. The overall percentage growth inhibition of leukemia cell lines was 42% and 41% when treated with compounds 7a and 7d, respectively. Results obtained in the present study would help developing potent cytotoxic compounds with specificity toward leukemia cancer. Keywords: oxime ethers; cholestane; leukemia; cell line assays; antiproliferative.

activity against a number of cell lines. It has been found that oximation at 3-, 6-, 7-, 16- and 17-positions of steroidal skeleton remains the most fruitful for antiproliferative effects. In particular, 6-hydroximinocholest-4-en-3-one 1 (Fig. 1) was the first steroidal oxime obtained from marine sponges Cinachyrella spp. as reported in 1997 [11]. Ample of its synthetic analogs were prepared and screened for in vitro cytotoxic activity [12 – 15]. Incorporation of oxime moiety at 3-, 6- and 7-positions resulted in good activity against Sk-Hep-1, H-292, PC-3, and Hey-1B cancer cell lines [9, 10]. The O-alkylation of steroidal oximes generally results in increased antiproliferative activity as is exemplified by several O-substituted derivatives of 17a-ethylnylandrostene oximes 2, estrane oximes 3, and androstane oxime 4 (Fig. 1). These oxime ethers synthesized in our laboratory shown significant in vitro antiproliferative activity in 60 cell line assay [8, 16]. These observations encouraged us to synthesise some new O-aminoalkylated derivatives of 3-hydroximinocholest-4-ene, which we report in the present study. In vitro antiproliferative screening of the obtained oxime ethers was carried out on 60 cell lines. The partition coefficient values of the O-alkylated steroidal derivatives were also estimated

1. INTRODUCTION Cancer has become a bulging cause of mortality worldwide with a majority of men suffering from prostate cancer, and women from breast cancer [1]. A plenty of new biomolecules have been synthesized till date for the treatment of several cancers. Among these molecules, steroidal moieties are gaining the attention of medici

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