ORIGINAL RESEARCH 17-Oximino-5-androsten-3b-yl esters: synthesis, antiproliferative activity, acute toxicity, and effect on serum androgen level Neelima Dhingra • Tilak Raj Bhardwaj • Neeraj Mehta • Tapas Mukhopadhyay • Ashok Kumar • Manoj Kumar Received: 11 September 2009 / Accepted: 20 July 2010 / Published online: 4 August 2010 Ó Springer Science+Business Media, LLC 2010 Abstract The 17-oximino-5-androsten-3b-yl esters (10a– 10j) were synthesized from commercially available (25R)- 5-Spirosten-3b-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiprolif- erative activity against prostate specific cancer cell line DU-145, acute toxicity, and effect on serum androgen level and were compared with Finasteride used as positive con- trol. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data, and biological eval- uation for the synthesized compounds are reported. Keywords Dihydrotestosterone  5-Alpha reductase enzyme  Benign prostatic hyperplasia  Steroids  Androgen Abbreviations BPH Benign prostatic hyperplasia T Testosterone DHT Dihydrotestosterone DCC Dicyclohexylcarbodiimide DU-145 Prostate cancer cell line MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] DMEM Dulbecco’s modified eagle medium Introduction Benign prostatic hyperplasia is the nonmalignant enlarge- ment of the prostate gland with increase in numbers of both epithelial and stromal cells within the periurethral transi- tion zone of the prostate, resulting in the constriction of prostatic urethra (Bullock and Andriole, 2006). The prev- alence increases to 50% by the age of 60 years and to 90% by the age of 85 years (Berry et al., 1984). Abnormal increase in the number of cells in prostate may result not only from increased cell proliferation but also from decreased level in programmed cell death (apoptosis) (Isaacs and Coffey, 1989). Number of available cytotoxic agents are able to induce apoptosis, and thus, can cause significant decrease in proliferation rate and are useful for the treatment of disease that involves abnormal or uncontrolled cell proliferation (Perez-Stable, 2006; Jakobsen et al., 2001; Brady et al., 2002; Garsky et al., 2001; Gediya et al., 2005; Gududuru et al., 2005). Treat- ments with standard cytotoxic agents do provide some palliative relief, but are associated with system toxicity. On the other hand, excessive production of dihydrotes- tosterone has been implicated in this pathological condition. Steroidal 5a-reductase is an NADPH-dependent enzyme that catalyzes the irreversible conversion of 4-en-3-oxosteroid, i.e., testosterone (T) to the corresponding 5a-H-3-oxoster- oid, i.e., dihydrotestosterone (DHT) (Fig. 1) (Bruchoksky et al., 1996). Two isozymes of 5a-reductase have been N. Dhingra  T. R. Bhardwaj  N. Mehta  M. Kumar (&) University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160-014, India e-mail: manoj_uips@pu.ac.in T. R. Bhardwaj I.S.F. College of Pharmacy, Ferozepur Road, Moga 142001, India T. Mukhopadhyay  A. Kumar National Centre for Human Genome Studies and Research, Panjab University, Chandigarh 160-014, India 123 Med Chem Res (2011) 20:817–825 DOI 10.1007/s00044-010-9393-3 MEDICINAL CHEMISTR Y RESEARCH