Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Samuel Silvestre
+ 1283 word(s) 1283 2021-04-28 06:34:23 |
2 format correct
Lindsay Dong
Meta information modification 1283 2021-04-29 04:47:21 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Silvestre, S. Bioactivity of Steroidal Arylidene Derivatives. Encyclopedia. Available online: https://encyclopedia.pub/entry/9163 (accessed on 01 July 2024).
Silvestre S. Bioactivity of Steroidal Arylidene Derivatives. Encyclopedia. Available at: https://encyclopedia.pub/entry/9163. Accessed July 01, 2024.
Silvestre, Samuel. "Bioactivity of Steroidal Arylidene Derivatives" Encyclopedia, https://encyclopedia.pub/entry/9163 (accessed July 01, 2024).
Silvestre, S. (2021, April 28). Bioactivity of Steroidal Arylidene Derivatives. In Encyclopedia. https://encyclopedia.pub/entry/9163
Silvestre, Samuel. "Bioactivity of Steroidal Arylidene Derivatives." Encyclopedia. Web. 28 April, 2021.
Bioactivity of Steroidal Arylidene Derivatives
Edit
This entry is adapted from the peer-reviewed paper 10.3390/molecules26072032

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems, in addition to their relevant bioactivity with potential pharmacological interest. 

steroids arylidenesteroids aldol condensation bioactivity heterocycles

1. Introduction

Steroids are natural products that share a 17-carbon-atom skeleton and are composed of four fused rings: three cyclohexanes (A, B, and C rings) and one cyclopentane (D ring). These compounds vary on the attached functional groups, their position, and configuration [1]. In addition, steroids represent a unique class of chemical products, playing an important role in several biological processes, being the most important group of regulatory and signaling molecules [2][3]. Usually, steroids are lipophilic and readily enter cells, being able to interact with nuclear receptors as well as with membrane proteins. Therefore, they are associated with most physiological functions and pathological conditions. In addition, due to their low toxicity, less vulnerability to multidrug resistance, and high bioavailability [4][5][6][7][8], steroid-based therapeutic drugs have called attention to the scientific academia and industry for a long time.

Due to their relevance, several modified steroids have been synthesized and biologically evaluated, being verified that their relevant pharmacological properties depend on the structural features of the steroidal four-ring skeleton and side-chain [5][9]. In fact, even a minor structural variation on the steroidal nucleus can lead to marked changes in their physiological activity [10]. Therefore, aiming to improve their pharmacological properties and/or develop compounds with different bioactivities, structural modifications of steroids have been an important focus of research over the last decades [11][12][13][14][15].

2. Synthetic Approaches to Prepare Arylidene Steroidal Derivatives

Arylidenesteroids are usually obtained through an aldol condensation between a steroid and an aldehyde. In an aldol condensation, an enol or enolate reacts with a carbonyl in the presence of an acid or base catalyst to form a β-hydroxyaldehyde or a β-hydroxyketone, followed by dehydration to afford a conjugated enone [16]. In general, the reactions to prepare arylidenesteroids occur at room temperature (RT), under basic catalysis, and the solvent is, in most cases, methanol (MeOH) or ethanol (EtOH) (Figure 1).

Molecules 26 02032 g001 550

Figure 1. Claisen–Schmidt condensation to prepare 16E- and 21E-arylidenesteroids.

3. Bioactivity of 2- and 16E-arylideneandrostane Derivatives

The 16E-arylideneandrostane steroidal skeleton has emerged as a relevant template to develop potential anticancer agents. In addition to cytotoxic effects, several studies reported other biological activities, such as aromatase inhibition, anti-inflammatory, neuroprotective and skeletal muscle relaxing activities and tissue-selective androgen receptor modulator effects [17][18][19].  A selection of the most relevant 16E-arylideneandrostane derivatives is presented in Table 1. 

Table 1. Examples of relevant bioactive 2- and 16E-arylideneandrostane derivatives. Positive controls, when shown, are identified by (+) symbol.

Compound Bioactivity Data Ref.
Molecules 26 02032 i001
2		 Antiproliferative activity (IC50 μM) [11]
Cell line 2 5-FU (+)
HepG2 9.10 10.59
MCF-7 9.18 28.11
Cell cycle arrest at G2 phase in HepG2
Molecules 26 02032 i002
3		 Antiproliferative activity (IC50 ± SEM μM) [20]
Cell line 3 Etoposide (+)
KB 0.6 ± 2.0 2.8 ± 16.8
T47-D 1.7 ± 14.8 1.2 ± 8
Molecules 26 02032 i003
4		 Antiproliferative activity (IC50 μM) [21]
Cell line 4
CCRF-CEM 3.94
K-562 2.61
RPMI-8226 6.90
SR 1.79
Molecules 26 02032 i004
5		 Antiproliferative activity (IC50 μM ± SD μM) [22]
Cell line 5 Cis (+)
HT-29 1.2 ± 0.4 66 ± 2
Molecules 26 02032 i005
6		 Cytotoxic activity–in vivo hollow fiber assay (score) [18]
  6 Taxol (+)
I.P. 2 Data not shown
S.C. 8
Molecules 26 02032 i006
7		 Cytotoxic activity–in vivo hollow fiber assay (score) [23]
  7 Taxol (+)
I.P. 12 Data not shown
S.C. 8
Molecules 26 02032 i007
8		 Aromatase inhibitory activity (IC50 μM) [24]
8 Aminoglutethimide (+)
5.2 28.5
Molecules 26 02032 i008
9		 Aromatase inhibitory activity (IC50 μM) [24]
9 Aminoglutethimide (+)
6.4 28.5
Molecules 26 02032 i009
10		 Aromatase inhibitory activity (IC50 μM) [25]
10 Aminoglutethimide (+)
4.4 28.5
Molecules 26 02032 i010
11		 Aromatase inhibitory activity (IC50 μM) [25]
11 Aminoglutethimide (+)
2.4 28.5
Molecules 26 02032 i011
12		 Anti-inflammatory activity
TNF-α levels (pg.mg−1protein ± SD)		 [26]
12 CEL (+) DEX (+)
88.6 ± 1.8 68.2 ± 1.1 89.6 ± 2.0
Molecules 26 02032 i012
13		 Anti-inflammatory activity (IC50 μM)
(NO release of LPS-activated mouse microglial cell line BV2)		 [27]
13 Minocycline (+)
2.69 5.97
Molecules 26 02032 i013
14		 Anti-inflammatory activity (IC50 μM)
(NO release of LPS-activated mouse microglial cell line BV2)		 [27]
14 Minocycline (+)
3.28 5.97

4. Bioactivity of 21E-arylidenepregnene Derivatives

Arylidenesteroidal derivatives of progesterone and pregnenolone and other similar pregnanes constitute a smaller group than arylideneandrostanes, and they have mainly been studied as potential antitumoral agents. Of these, the most potent arylidenepregnene derivatives reported until now are presented in Table 2.

Table 2. The most active 21E-arylidenepregnene derivatives. Positive controls, when shown, are identified by (+) symbol.

Compound Bioactivity Data Ref.
Molecules 26 02032 i014
15		 Antiproliferative activity (IC50 μM) [28]
Cell line 15
HCT-15 0.81
Molecules 26 02032 i015
16		 Antiproliferative activity (IC50 μM) [28]
Cell line 16
MCF-7 0.60
Molecules 26 02032 i016
17		 Antiproliferative activity
Growth inhibition (%)		 [17]
Cell line 17 Cis (+)
HeLa 58 99
MCF-7 64 88
Molecules 26 02032 i017
18		 Antimicrobial activity
Zone of inhibition (mm)		 [29]
Gram positive 18 AMP (+)
Streptococcus pneumoniae 30 20
Staphylococcus aureus 24 22

5. Bioactivity of 16E-arylidenoestrone and 16E-arylidenoestradiol Derivatives

It is well known that estrogenic hormones have an important contribution to estrogen-dependent diseases, being breast cancers primarily initiated and stimulated by estrogens the majority of these conditions [30]. Consequently, the structural modification of estrone and estradiol in different positions to prepare bioactive compounds in this context has been the focus of intensive research.

Table 3. The most active 16E-arylidenoestrone and -estradiol derivatives. Positive controls, when shown, are identified by (+) symbol.

Compound Bioactivity Data Ref.
Molecules 26 02032 i018
19		 17β-HSD1 inhibitory activity (IC50 μM) [31]
19 Estradiol (+)
3.4 7.3
Molecules 26 02032 i019
20		 17β-HSD inhibitory activity (% at 10 μM) [32]
20
Type 1 Type 2
72 13
Molecules 26 02032 i020
21		 Tumor weight reduction (%)
Human breast cancer (MCF-7) xenografts models		 [33]
21
(45 mg/kg/day)		 2ME (+) (45 mg/kg/day)
About 50%
Significative reduction compared with negative control		 About 50%
Significative reduction compared with negative control

Of these prepared compounds, steroid 21 (Table 3) showed a potent antiangiogenic activity. Moreover, further studies suggested that this compound suppresses the tumor growth in about 50% in human breast cancer (MCF-7) xenograft models without relevant side effects. The action mechanism studies suggested that steroid 21 targeted the epithelial to mesenchymal transition process in MCF-7 cells and inhibited human umbilical vein endothelial cells (HUVEC) migration, contributing to angiogenesis interruption [33].

6. Importance of Steroidal Arylidene Derivatives as Synthetic Intermediates of Bioactive Molecules

In addition to their biological activity, steroidal arylidenes are also versatile synthetic intermediates in the preparation of other bioactive structures. In fact, these steroids have been used in the introduction of diverse chemical groups present in bioactive compounds, such as oximes, hydroxyl and hydrazones [28][34][35][36][37], and are particularly useful in several heterocyclization reactions. In this context, over the years, a large number of bioactive heterocyclic steroidal derivatives have been synthesized, and some of them are already being clinically used [38][39]. Interestingly, diverse heterocyclic compounds, including arylpyrazolines and pyrazoles, arylpyrimidines, oxindoles, pyridones and pyridines as well as spiro-pyrrolidines were prepared from arylidenesteroids [4][13][40][41][42][43][29][37][44][45][46][47][48][49][50][51][52][53][54]. The most promising steroidal derivatives prepared from arylidenesteroids that have been reported until the moment are presented in Table 4. 

Table 4. The most active steroidal derivatives obtained from arylidenesteroids. Positive controls, when shown, are identified by (+) symbol.

Compound Bioactivity Data Ref.
Molecules 26 02032 i021
24		 Antiproliferative activity (IC50 μM) [4]
Cell line 24
HT-29 0.24
HCT-15 0.25
Molecules 26 02032 i022
25		 Antiproliferative activity (IC50 μM) [41]
Cell line 25 5-FU (+)
HepG-2 5.41 >100
Huh-7 5.65 >95
SGC-790 10.64 >100
Molecules 26 02032 i023
26		 5AR-1 Inhibition (IC50 ± SEM μM) [44]
26 Finasteride (+)
14.50 ± 0.48 21.6 ± 0.62
Molecules 26 02032 i024
27		 5AR-2 Inhibition (IC50 ± SEM μM) [44]
27 Finasteride (+)
13.90 ± 0.75 15.4 ± 0.58
Molecules 26 02032 i025
28		 5AR-2 Inhibition (IC50 ± SEM μM) [44]
28 Finasteride (+)
14.20 ± 0.75 15.4 ± 0.58
Molecules 26 02032 i026
29		 5AR-2 Inhibition (IC50 ± SEM nM) [46]
29 Finasteride (+)
7.30 ± 0.62 2.4 ± 0.15
Molecules 26 02032 i027
30		 5AR-2 Inhibition (IC50 ± SEM nM) [46]
30 Finasteride (+)
8.20 ± 0.55 2.4 ± 0.58
Molecules 26 02032 i028
31		 Antiproliferative activity (IC50 μg.mL−1) [13]
Cell line 31 5-FU (+) Cis (+)
NCI-H460 10.30 2.48 0.699
HeLa 12.50 0.887 2.03
Cell cycle arrest at S phase in HeLa cells
Molecules 26 02032 i029
32		 Antiproliferative activity (IC50 μM) [43]
Cell line 32 5-FU (+)
SMMC-7721 4.30 9.78
MCF-7 2.06 7.54
Molecules 26 02032 i030
33		 Antiproliferative activity (IC50 ± SEM μM) [43]
Cell line 33 5-FU (+)
SMMC-7721 6.05 ± 0.48 9.78 ± 0.99
MGC-803 5.79 ± 0.76 6.92 ± 0.35
Cell cycle arrest at G2/M phase in MGC cells
Molecules 26 02032 i031
34		 Antiproliferative activity (IC50 ± SEM μM) [43]
Cell line 34 5-FU (+)
SMMC-7721 0.71 ± 0.11 9.78 ± 0.99
Molecules 26 02032 i032
35		 Antiproliferative activity (IC50 μM) [37]
Cell line 35 DOX (+)
MDA-MB 231 0.91 1.23
Molecules 26 02032 i033
36		 Osteoanabolic activity and tissue-selectivity
(% of the effect of DHT)		 [55]
OVX 36 DHT
BRF 120 100
ORX
VP 3 100
SV 21 100
Molecules 26 02032 i034
37		 Cytotoxic activity-in vivo hollow fiber assay (score) [18]
  37 Taxol (+)
I.P. 4 Data not shown
S.C. 6
Molecules 26 02032 i035
38		 Antiproliferative activity
Cell growth (%)		 [56]
Cell line 38
NCI-H460 −44
MFC-7 −44
SF-268 −79
Molecules 26 02032 i036
39		 Antiproliferative activity
Cell growth (%)		 [36]
Cell line 39
NCI-H460 −11
MCF-7 5
SF-268 −8

7. Summary

Steroids constitute an important group of structurally related natural, semi-synthetic, and synthetic compounds with remarkable functions, including regulatory and signaling activities. In the last three decades, steroidal arylidene derivatives have been prepared and screened for a range of biological activities and used as synthetic intermediates, with special attention to bioactive heterocyclic steroids. In conclusion, due to the straightforward synthesis of arylidenesteroids and their bioactivity, as well as the inherent chemical reactivity of α,β-unsaturated ketones, useful in the preparation of other derivatives, this class of compounds has been of high interest in the last years.

References

  1. Lednicer, D. Steroid Chemistry at a Glance; Wiley: Hoboken, NJ, USA, 2011; ISBN 9780470660850.
  2. Burger, A.; Abraham, D.J.; Rotella, D.P. Burger’s Medicinal Chemistry, Drug Discovery and Development; Wiley: Hoboken, NJ, USA, 2010; Volume 7, ISBN 9780470770085.
  3. Latham, K.A.; Zamora, A.; Drought, H.; Matejuk, A.; Offner, H.; Edward, F. Estradiol Treatment Redirects the Isotype of the Autoantibody Response and Prevents the Development of Autoimmune Arthritis. J. Immunol. 2003, 171, 5820–5827.
  4. Banday, A.H.; Mir, B.P.; Lone, I.H.; Suri, K.A.; Kumar, H.M.S. Studies on Novel D-Ring Substituted Steroidal Pyrazolines as Potential Anticancer Agents. Steroids 2010, 75, 805–809.
  5. Tantawy, M.A.; Nafie, M.S.; Elmegeed, G.A.; Ali, I.A.I. Auspicious Role of the Steroidal Heterocyclic Derivatives as a Platform for Anti-Cancer Drugs. Bioorg. Chem. 2017, 73, 128–146.
  6. Vil, V.A.; Terent, A.O.; Savidov, N.; Gloriozova, T.A. Hydroperoxy Steroids and Triterpenoids Derived from Plant and Fungi: Origin, Structures and Biological Activities. J. Steroid Biochem. Mol. Biol. 2019, 190, 76–87.
  7. Dembitsky, V.M. Progress in Lipid Research Antitumor and Hepatoprotective Activity of Natural and Synthetic Neo Steroids. Prog. Lipid Res. 2020, 79, 101048.
  8. Xiao, J.; Gao, M.; Fei, B.; Huang, G.; Diao, Q. Fitoterapia Nature-Derived Anticancer Steroids Outside Cardica Glycosides. Fitoterapia 2020, 147, 104757.
  9. Na, M.S.; Tantawy, M.A.; Elmgeed, G.A. Screening of Different Drug Design Tools to Predict the Mode of Action of Steroidal Derivatives as Anti-Cancer Agents. Steroids 2019, 152.
  10. Lemke, T.L.; Williams, D.A.; Roche, V.F.; Zito, S.W. Foye’s Principles of Medicinal Chemistry, 7th ed.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2012.
  11. Huang, X.; Shen, Q.; Zhang, H.; Li, J.; Tian, Y.; Quan, Z. Design and Synthesis of Novel Dehydroepiandrosterone Analogues as Potent Antiproliferative Agents. Molecules 2018, 23, 2243.
  12. Acharya, P.C.; Bansal, R.; Kharkar, P.S.; Res, D.; Bansal, R. Hybrids of Steroid and Nitrogen Mustard as Antiproliferative Agents: Synthesis, in Vitro Evaluation and in Silico Inverse Screening Authors. Drug Res. (Stuttg). 2017.
  13. Fan, N.; Tang, J.; Li, H.; Li, X.; Luo, B.; Gao, J. Synthesis and Cytotoxic Activity of Some Novel Steroidal C-17 Pyrazolinyl Derivatives. Eur. J. Med. Chem. 2013, 69, 182–190.
  14. Gogoi, J.; Bezbaruah, P.; Saikia, P.; Goswami, J.; Gogoi, P.; Boruah, R.C. Synthesis of a Novel Class of Steroidal Tetrazolo[1,5-a]Pyridines Via Intramolecular 1,3-Dipolar Cycloadditions. Tetrahedron Lett. 2012, 53, 1497–1500.
  15. Chowdhury, P.; Borah, J.M.; Goswami, P.; Das, A.M. A Convenient Synthesis of the Side Chain of Loteprednol Etabonate - an Ocular Soft Corticosteroid from 20-Oxopregnanes Using Metal-Mediated Halogenation as a Key Reaction. Steroids 2011, 76, 497–501.
  16. Furniss, B.S.; Hannaford, A.J.; Smith, P.W.G.; Tatchell, A.R. Vogel’s Textboom of Practical Organic Chemistry, 5th ed.; Pearson: Delhi, India, 1989.
  17. Fan, N.; Han, Y.; Li, Y.; Gao, J.; Tang, J. Synthesis of Novel 4′-Acylamino Modified 21E-Benzylidene Steroidal Derivatives and Their Cytotoxic Activities. Steroids 2017, 123, 20–26.
  18. Chattopadhaya, R.; Jindal, D.P.; Minu, M.; Gupta, R. Synthesis and Cytotoxic Studies of Hydroximino Derivatives of Some 16E-Arylidenosteroids. Arzneim. Forshung Drug Res. 2004, 556, 551–556.
  19. Longley, D.B.; Harkin, D.P.; Johnston, P.G. 5-Fluorouracil: Mechanisms of Action and Clinical Strategies. Nat. Rev. Cancer 2003, 3, 330–338.
  20. Vosooghi, M.; Yahyavi, H.; Divsalar, K.; Shamsa, H.; Kheirollahi, A.; Safavi, M.; Ardestani, S.K.; Sadeghi-Neshat, S.; Mohammadhosseini, N.; Edraki, N.; et al. Synthesis and in Vitro Cytotoxic Activity Evaluation of (E)-16-(Substituted Benzylidene) Derivatives of Dehydroepiandrosterone. Daru 2013, 21, 34.
  21. Bansal, R.; Acharya, P.C. Synthesis and Antileukemic Activity of 16E-[4-(2-Carboxy)Ethoxybenzylidene]-Androstene Amides. Steroids 2012, 77, 552–557.
  22. Narváez-Pita, X.; Rheingold, A.L.; Meléndez, E. Ferrocene-Steroid Conjugates: Synthesis, Structure and Biological Activity. J. Organomet. Chem. 2017, 846, 113–120.
  23. Bansal, R.; Guleria, S. Synthesis of 16E-[3-Methoxy-4-(2-Aminoethoxy)Benzylidene]Androstene Derivatives as Potent Cytotoxic Agents. Steroids 2008, 73, 1391–1399.
  24. Bansal, R.; Thota, S.; Karkra, N.; Minu, M.; Zimmer, C.; Hartmann, R.W. Synthesis and Aromatase Inhibitory Activity of Some New 16E-Arylidenosteroids. Bioorg. Chem. 2012, 45, 36–40.
  25. Bansal, R.; Guleria, S.; Thota, S.; Hartmann, R.W.; Zimmer, C. Synthesis of Imidazole-Derived Steroidal Hybrids as Potent Aromatase Inhibitors. Med. Chem. Res. 2013, 22, 692–698.
  26. Singh, R.; Bansal, R. Investigations on 16-Arylideno Steroids as a New Class of Neuroprotective Agents for the Treatment of Alzheimer’s and Parkinson’s Diseases. ACS Chem. Neurosci. 2016.
  27. Zhu, L.; Yang, Y.; Gao, P.; An, X.; Sun, Y.; Sun, X.; Hou, Y.; Shan, L. Synthesis and Anti-Inflammatory Activity Evaluation of 2-Dehydroepiandrosterone Benzene Methyl Derivatives. Chinese J. Org. Chem. 2019, 39, 2625–2631.
  28. Banday, A.H.; Akram, S.M.M.; Shameem, S.A. Benzylidine Pregnenolones and Their Oximes as Potential Anticancer Agents: Synthesis and Biological Evaluation. Steroids 2014, 84, 64–69.
  29. Abood, N.K.; Ibraheem, H.H. Synthesis, Characterize and Antimicrobial Study of New Chalcones and Pyrazole Derivatives from Progesterone. Int. J. Sci. Res. 2016, 5, 2319–7064.
  30. Bernstein, L.; Ross, R.K. Endogenous Hormones and Breast Cancer Risk. Epidemiol. Rev. 1993, 15, 48–65.
  31. Poirier, D.; Chang, H.; Azzi, A.; Boivin, R.P.; Lin, S. Estrone and Estradiol C-16 Derivatives as Inhibitors of Type 1 17b-Hydroxysteroid Dehydrogenase. Mol. Cell. Endocrinol. 2006, 248, 236–238.
  32. Allan, G.M.; Lawrence, H.R.; Cornet, J.; Bubert, C.; Fischer, D.S.; Vicker, N.; Smith, A.; Tutill, H.J.; Purohit, A.; Day, J.M.; et al. Modification of Estrone at the 6, 16, and 17 Positions: Novel Potent Inhibitors of 17 -Hydroxysteroid Dehydrogenase Type 1. J. Med. Chem. 2006, 49, 1325–1345.
  33. Wang, C.; Li, L.; Fu, D.; Qin, T.; Ran, Y.; Xu, F.; Du, X. Discovery of Chalcone-Modified Estradiol Analogs as Antitumour Agents That Inhibit Tumour Angiogenesis and Epithelial to Mesenchymal Transition. Eur. J. Med. Chem. 2019, 176, 135–148.
  34. Kolo, A.M.; İpek, E.; Çapan, İ.; Servi, S. Synthesis of Heterocyclic-Substituted Novel Hydroxysteroids with Regioselective and Stereoselective Reactions. J. Heterocycl. Chem. 2018, 55, 492–497.
  35. Thamotharan, S.; Parthasarathi, V.; Gupta, R. Two Androst-5-Ene Derivatives: 16-[4-(3-Chloropropoxy)-3-Methoxybenzylidene]-17-Oxoandrost-5-En-3β-Ol and 16-[3-Methoxy-4-(2-Pyrrolidin-1-Ylethoxy)Benzylidene]-3β-Pyrrolidinoandrost-5-En-17β-Ol Monohydrate. Acta Crystallogr. Sect. C Cryst. Struct. Commun. 2004, 60, 75–78.
  36. Dubey, S.; Piplani, P.; Jindal, D.P. Synthesis and Evaluation of Some 16-Benzylidene Substituted 3,17-Dioximino Androstene Derivatives as Anticancer Agents. Lett. Drug Des. Discov. 2005, 2, 537–545.
  37. Choudhary, M.I.; Alam, M.S.; Yousuf, S.; Wu, Y.; Lin, A.; Shaheen, F. Pregnenolone Derivatives as Potential Anticancer Agents. Steroids 2011, 76, 1554–1559.
  38. Bryce, A.; Ryan, C.J. Development and Clinical Utility of Abiraterone Acetate as an Androgen Synthesis Inhibitor. Clin. Pharmacol. Ther. 2009, 91, 101–108.
  39. Bastos, D.A.; Antonarakis, E.S. Galeterone for the Treatment of Advanced Prostate Cancer: The Evidence to Date. Drug Des. Devel. Ther. 2016, 10, 2289–2297.
  40. Huang, L.-H.; Zheng, Y.-F.; Lu, Y.-Z.; Song, C.-J.; Wang, Y.-G.; Yu, B.; Liu, H.-M. Synthesis and Biological Evaluation of Novel Steroidal[17,16-d][1,2,4]Triazolo[1,5-a]Pyrimidines. Steroids 2012, 77, 710–715.
  41. Ke, S.; Shi, L.; Zhang, Z.; Yang, Z. Pyrimidines Derived from Dehydroepiandrosterone: A Convenient Synthesis, Antiproliferation Activity, Structure-Activity Relationships, and Role of Heterocyclic Moiety. Nat. Publ. Gr. 2017, 7, 1–7.
  42. Mótyána, G.; Molnár, B.; Wölfling, J.; Frank, É. Microwave-Assisted Stereoselective Heterocyclization to Novel Ring D-Fused Arylpyrazolines in the Estrone Series. Molecules 2019, 24, 1–15.
  43. Yu, B.; Shi, X.; Qi, P.; Yu, D.; Liu, H. Design, Synthesis and Biological Evaluation of Novel Steroidal Spiro-Oxindoles as Potent Antiproliferative Agents. J. Steroid Biochem. Mol. Biol. 2014, 141, 121–134.
  44. Banday, A.H.; Shameem, S.A.; Jeelani, S. Steroidal Pyrazolines and Pyrazoles as Potential 5α-Reductase Inhibitors: Synthesis and Biological Evaluation. Steroids 2014, 92, 13–19.
  45. Singh, R.; Thota, S.; Bansal, R. Studies on 16,17-Pyrazoline Substituted Heterosteroids as Anti-Alzheimer and Anti-Parkinsonian Agents Using LPS Induced Neuroinflammation Models of Mice and Rats. ACS Chem. Neurosci. 2017.
  46. Banday, A.H.; Shameem, S.A.; Banday, J.A.; Ganaie, B.A. Synthesis, 17α-Hydroxylase-C 17,20-Lyase Inhibitory and 5AR Reductase Activity of Novel Pregnenolone Derivatives. Anticancer. Agents Med. Chem. 2018, 18, 1919–1926.
  47. El-Naggar, M.; Amr, A.E.E.; Fayed, A.A.; Elsayed, E.A. Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600E BRAF of Synthesized Substituted Estrone Candidates. Molecules 2019, 24, 2054.
  48. Amr, A.E.E.; Abdel-latif, N.A.; Abdalla, M.M. Synthesis and Antiandrogenic Activity of Some New 3-Substituted Androstano [17,16-c]-5′-Aryl-Pyrazoline and Their Derivatives. Bioorg. Med. Chem. 2006, 14, 373–384.
  49. Shi, Y.; Wang, B.; Shi, X.; Zhao, Y. Synthesis and Biological Evaluation of New Steroidal Pyridines as Potential Anti-Prostate Cancer Agents. Eur. J. Med. Chem. 2018, 145, 11–22.
  50. Amr, A.E.E.; Elsayed, E.A.; Al-omar, M.A.; Eldin, H.O.B.; Nossier, E.S.; Abdallah, M.M. Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives. Molecules 2019, 24, 416.
  51. Babu, A.R.S.; Raghunathan, R. An Easy Access to Novel Steroidal Dispiropyrrolidines through 1, 3-Dipolar Cycloaddition of Azomethine Ylides. Tetrahedron Lett. 2008, 49, 4618–4620.
  52. Gavaskar, D.; Babu, A.R.S.; Raghunathan, R.; Dharani, M.; Balasubramanian, S. An Expedient Sequential One-Pot Four Component Synthesis of Novel Steroidal Spiro-Pyrrolidine Heterocycles in Ionic Liquid. Steroids 2016, 109, 1–6.
  53. Mótyána, G.; Gopisetty, M.K.; Kiss-Faludy, R.E.; Kulmány, Á.; Zupkó, I.; Frank, É.; Kiricsi, M. Anti-Cancer Activity of Novel Dihydrotestosterone-Derived Ring A-Condensed Pyrazoles on Androgen Non-Responsive Prostate Cancer Cell Lines. Int. J. Mol. Sci. 2019, 20, 2170.
  54. Iványi, Z.; Szabó, N.; Wölfling, J.; Szécsi, M.; Julesz, J.; Schneider, G. Novel Series of 17β-Pyrazolylandrosta-5,16-Diene Derivatives and Their Inhibitory Effect on 17α-Hydroxylase/C17,20-Lyase. Steroids 2012, 77, 1152–1159.
  55. Mitchell, H.J.; Dankulich, W.P.; Hartman, G.D.; Prueksaritanont, T.; Schmidt, A.; Vogel, R.L.; Bai, C.; Mcelwee-witmer, S.; Zhang, H.Z.; Chen, F.; et al. Design, Synthesis, and Biological Evaluation of 16-Substituted 4-Azasteroids as Tissue-Selective Androgen Receptor Modulators (SARMs). J. Med. Chem. 2009, 52, 4578–4581.
  56. Dubey, S.; Jindal, D.P.; Piplani, P. Synthesis and Antineoplastic Activity of Some 16-Benzylidene Substituted Steroidal Oximes. Indian J. Chem. 2005, 44, 2126–2137.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Samuel Silvestre
View Times: 541
Revisions: 2 times (View History)
Update Date: 29 Apr 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback