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The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect

Yıl 2023, Cilt: 27 Sayı: 2, 936 - 947, 27.06.2025

Zeynep Ağlamış Nil Bita Entezari Ökeer , Sibel Süzen , Hande Gürer-orhan

Öz

Melatonin (MLT) is a hormone that is secreted from pineal gland and regulates the circadian rhythm. It is
reported to have anticancer effects in hormone dependent breast cancer via endocrine modulation, namely by
antagonising the estrogen receptor (ER) or by inhibiting aromatase enzyme. However, its use is restricted because of its
short half-life and poor bioavailability. Therefore, indole derived MLT analogues were synthesized previously, and they
were shown to have potential antioxidant and anticancer effects. The present research is aimed to investigate the
potential of MLT and its two newly synthesized analogues (M6 and M20) on steroidogenesis pathway by using an
OECD validated in vitro method, H295R steroidogenesis assay (TG-456 test guideline). The compounds were incubated
with H295R, human adenocarcinoma cells, for 48 hours and the hormone levels (testosterone; T and estradiol; E2) were
detected by LC-MS/MS. The partial validation of the method was performed by using reference compounds forskolin,
prochloraz, letrozole and ketoconazole. MLT decreased both E2 and T levels and its effect on E2 levels were dose
dependent. On the other hand, M6 and M20 showed biphasic effects on both hormone levels. None of the compounds
decreased H295R cell viability. These results demonstrate that depending on the use and the dose of these melatonin
analogues, their potential effects on hormone production can result either in a therapeutical effect (such as anticancer
agent) or a non-targeted endocrine related adverse effect when used as a pharmaceutical.

Anahtar Kelimeler

Steroidogenesis melatonin analogues therapeutical effect endocrine related adverse effect LC-MS/MS

Kaynakça

  • Reiter RJ. The melatonin rhythm: both a clock and a calendar. Experientia. 1993; 49 (8): 654-664. https://doi.org/10.1007/BF01923947
  • Kostoglou-Athanassiou I. Therapeutic applications of melatonin. Therapeutic advances in endocrinology and metabolism. 2013; 4(1): 13-24. https://doi.org/10.1177/2042018813476084
  • Sánchez-Barceló EJ, Cos S, Mediavilla D, Martínez-Campa C, González A, Alonso-González C. Melatonin-estrogen interactions in breast cancer. Journal of pineal research. 2005; 38 (4): 217-222. https://doi.org/10.1111/j.1600- 079X.2004.00207.x
  • Cos S, González A, Martínez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-Barceló EJ. Estrogen-signaling pathway: A link between breast cancer and melatonin oncostatic actions. Cancer detection and prevention. 2006; 30 (2): 118-128. https://doi.org/10.1016/j.cdp.2006.03.002
  • Di Bella G, Mascia F, Gualano L, Di Bella L. Melatonin anticancer effects: review. International journal of molecular sciences. 2013; 14 (2): 2410-2430. https://doi.org/10.3390/ijms14022410
  • Fraschini F, Demartini G, Esposti D, Scaglione F. Melatonin involvement in immunity and cancer. Biological signals. 1998; 7 (1): 61-72. https://doi.org/10.1159/000014529
  • Hill SM, Frasch T, Xiang S, Yuan L, Duplessis T, Mao L. Molecular mechanisms of melatonin anticancer effects. Integrative cancer therapies. 2009; 8 (4): 337-346. https://doi.org/10.1177/1534735409353332
  • Cos S, Martínez-Campa C, Mediavilla MD, Sánchez-Barceló EJ. Melatonin modulates aromatase activity in MCF-7 human breast cancer cells. Journal of pineal research. 2005; 38 (2): 136-142. https://doi.org/10.1111/j.1600- 079X.2004.00186.x
  • Chottanapund S, Van Duursen MBM, Navasumrit P, Hunsonti P, Timtavorn S, Ruchirawat M, Berg MVd. Anti- aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts. Toxicology in vitro: an international journal published in association with BIBRA. 2014; 28 (7): 1215-1221. https://doi.org/10.1016/j.tiv.2014.05.015
  • Martínez-Campa C, González A, Mediavilla MD, Alonso-Gonzalez C, Alvarez-Garcia V, Sanchez-Barcelo EJ, Cos S. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells. British journal of cancer. 2009; 101 (9): 1613-1619. https://doi.org/10.1038/sj.bjc.6605336
  • Grigg-Damberger MM, Ianakieva D. Poor quality control of over-the-counter melatonin: what they say is often not what you get. Journal of clinical sleep medicine: JCSM : official publication of the American Academy of Sleep Medicine. 2017; 13 (2): 163. https://doi.org/10.5664/jcsm.6434
  • Rajaratnam SMW, Cohen DA, Rogers NL. Melatonin and melatonin analogues. Sleep Medicine Clincs. 2009; 4 (2): 179-193. https://doi.org/10.1016/j.jsmc.2009.02.007
  • Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica; the fate of foreign compounds in biological systems. 2019; 49 (5): 549-556. https://doi.org/10.1080/00498254.2018.1482029
  • Gurer-Orhan H, Suzen S. Melatonin, its metabolites and its synthetic analogs as multi-faceted compounds: antioxidant, prooxidant and ınhibitor of bioactivation reactions. Current medicinal chemistry. 2015; 22 (4): 490-499. http://doi.org/10.2174/0929867321666141215095259
  • Shirinzadeh H, Neuhaus E, Ince-Erguc E, Tascioglu-Aliyev A, Gurer-Orhan H, Suzen S. New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorganic chemistry. 2020; 104219. https://doi.org/10.1016/j.bioorg.2020.104219
  • Sanderson JT. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicological sciences: an official journal of the Society of Toxicology. 2006; 94 (1): 3-21. https://doi.org/10.1093/toxsci/kfl051
  • OECD Test No. 456: H295R Steroidogenesis Assay. https://read.oecd-ilibrary.org/environment/test-no-456-h295r- steroidogenesis-assay_9789264122642-en#page1. (accessed April 29, 2022).
  • Albert O, Desdoits-Lethimonier C, Lesné L, Legrand A, Guille F, Bensalah K, Dejucq-Rainsford N, Jegou B. Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro. Human reproduction (Oxford, England). 2013; 28 (7): 1890-1898. https://doi.org/10.1093/humrep/det112
  • Stukenborg JB, Mitchell RT, Söder O. Endocrine disruptors and the male reproductive system. Clinical endocrinology & metabolism. 2021; 35 (5), 101567. https://doi.org/10.1016/j.beem.2021.101567
  • Craig ZR, Wang W, Flaws JA. Endocrine-disrupting chemicals in ovarian function: Effects on steroidogenesis, metabolism and nuclear receptor signaling. Reproduction (Cambridge, England). 2011; 142: 633-646. https://doi.org/10.1530/REP-11-0136
  • Nielsen FK, Hansen CH, Fey JA, Hansen M, Jacobsen NW, Halling-Sorensen B, Björklund E, Styrishave B. H295R cells as a model for steroidogenic disruption: A broader perspective using simultaneous chemical analysis of 7 key steroid hormones. Toxicology in vitro: an international journal published in association with BIBRA. 2012; 26 (2): 343- 350. https://doi.org/10.1016/j.tiv.2011.12.008
  • OECD Work Related to Endocrine Disrupters. https://www.oecd.org/chemicalsafety/testing/oecdworkrelatedtoendocrinedisrupters.htm (accessed April 29, 2022).
  • Haggard DE, Karmaus AL, Martin MT, Judson RS, Setzer RW, Friedman KP. High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis. Toxicological sciences: an official journal of the Society of Toxicology. 2018; 162 (2): 509-534. https://doi.org/10.1093/toxsci/kfx274
  • ATCC. NCI-H295R. https://www.atcc.org/products/crl-2128 (accessed June 15, 2022).
  • Higley EB, Newsted JL, Zhang X, Giesy JP, Hecker M. Assessment of chemical effects on aromatase activity using the H295R cell line. Environmental science and pollution research international. 2010; 17 (5): 1137-1148. https://doi.org/10.1007/s11356-009-0285-3
  • Hecker M, Giesy JP. Novel trends in endocrine disruptor testing: The H295R Steroidogenesis Assay for identification of inducers and inhibitors of hormone production. Analytical and bioanalytical chemistry. 2008; 390 (1): 287-291. https://doi.org/10.1007/s00216-007-1657-5
  • Maglich JM, Kuhn M, Chapin RE, Pletcher MT. More than just hormones: H295R cells as predictors of reproductive toxicity. Reproductive toxicology. 2014; 45: 77-86. https://doi.org/10.1016/j.reprotox.2013.12.009
  • Chase JE, Gidal BE. Melatonin: Therapeutic use in sleep disorders. The Annals of pharmacotherapy. 1997; 31 (10): 1218-1226. https://doi.org/10.1177/106002809703101015
  • Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Mühlbauer E. Melatonin and type 2 diabetes – a possible link?. Journal of pineal research. 2007; 42 (4): 350-358. https://doi.org/10.1111/j.1600-079X.2007.00426.x
  • Kiefer T, Ram PT, Yuan L, Hill SM. Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells. Breast cancer research and treatment 2002; 71 (1): 37-45. https://doi.org/10.1023/A:1013301408464
  • Cos S, Fernandez R, Güezmez A, Sãnchez-Barcelo EJ. Influence of melatonin on ınvasive and metastatic properties of mcf-7 human breast cancer cells. Cancer research. 1998; 58 (19): 4383-4390.
  • Hill SM, Belancio VP, Dauchy RT, Xiang S, Brimer S, Mao L, Hauch A, Lundberg PW, Summers W, Yuan L, Frasch T, Blask DE. Melatonin: an inhibitor of breast cancer. Endocrine-related cancer. 2015; 22 (3): R183-R204. https://doi.org/10.1530/ERC-15-0030
  • Hecker M, Hollert H, Cooper R, Vingguard AM, Akahori Y, Murphy M, Nellemann C, Higley E, Newsted J, Laskey J, Buckalew A, Grund S, Maletz S, Giesy J, Timm G. The OECD validation program of the H295R steroidogenesis assay: Phase 3. Final inter-laboratory validation study. Environmental science and pollution research international. 2018; 25 (15), 15265. https://doi.org/10.1007/s11356-010-0396-x
  • Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C. Melatonin: pharmacology, functions and therapeutic benefits. Current neuropharmacology. 2017; 15 (3): 434. http://doi.org/10.2174/1570159X14666161228122115
  • Darbre PD. Endocrine Disruption and Human Health. 1st ed, Reading, UK 2015. L
  • agarde F, Beausoleil C, Belcher SM, Belzunces LP, Emond C, Guerbet M, Rousselle C. Non-monotonic dose-response relationships and endocrine disruptors: A qualitative method of assessment. Environmental health: a global access science source. 2015; 14 (1): 1-15. http://doi.org/10.1186/1476-069X-14-13
  • Kaur K, Jaitak V. Recent Development in Indole Derivatives as Anticancer Agents for Breast Cancer. Anticancer Agents Med Chem. 2019;19(8):962-983. http://doi.org/10.2174/1871520619666190312125602
  • Sidhu JS, Singla R, Mayank, Jaitak V. Indole Derivatives as Anticancer Agents for Breast Cancer Therapy: A Review. Anticancer Agents Med Chem. 2015;16(2):160-73. http://doi.org/10.2174/1871520615666150520144217
  • Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica. 2019 May;49(5):549-556. https://doi.org/10.1080/00498254.2018.1482029
  • Shirinzadeh H, Neuhaus E, Ince-Erguc E, Tascioglu-Aliyev A, Gurer-Orhan H, Suzen S. New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorg Chem. 2020 Nov;104:104219. https://doi.org/10.1016/j.bioorg.2020.104219
  • Shirinzadeh H, Ince E, Westwell AD, Gurer-Orhan H, Suzen S. Novel indole-based melatonin analogues substituted with triazole, thiadiazole and carbothioamides: studies on their antioxidant, chemopreventive and cytotoxic activities. J Enzyme Inhib Med Chem. 2016 Dec;31(6):1312-21. https://doi.org/10.3109/14756366.2015.1132209
  • Öztürk-Ceylan Ö, MSc Thesis. Synthesis and biological activitie evaluation of new antimicrobial indole derivatives. Department of Biotechnology, Enstitute of Biotechnology, Ankara University, Keçiören, Ankara, Turkey, 2015.

Yıl 2023, Cilt: 27 Sayı: 2, 936 - 947, 27.06.2025

Zeynep Ağlamış Nil Bita Entezari Ökeer , Sibel Süzen , Hande Gürer-orhan

Öz

Kaynakça

  • Reiter RJ. The melatonin rhythm: both a clock and a calendar. Experientia. 1993; 49 (8): 654-664. https://doi.org/10.1007/BF01923947
  • Kostoglou-Athanassiou I. Therapeutic applications of melatonin. Therapeutic advances in endocrinology and metabolism. 2013; 4(1): 13-24. https://doi.org/10.1177/2042018813476084
  • Sánchez-Barceló EJ, Cos S, Mediavilla D, Martínez-Campa C, González A, Alonso-González C. Melatonin-estrogen interactions in breast cancer. Journal of pineal research. 2005; 38 (4): 217-222. https://doi.org/10.1111/j.1600- 079X.2004.00207.x
  • Cos S, González A, Martínez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-Barceló EJ. Estrogen-signaling pathway: A link between breast cancer and melatonin oncostatic actions. Cancer detection and prevention. 2006; 30 (2): 118-128. https://doi.org/10.1016/j.cdp.2006.03.002
  • Di Bella G, Mascia F, Gualano L, Di Bella L. Melatonin anticancer effects: review. International journal of molecular sciences. 2013; 14 (2): 2410-2430. https://doi.org/10.3390/ijms14022410
  • Fraschini F, Demartini G, Esposti D, Scaglione F. Melatonin involvement in immunity and cancer. Biological signals. 1998; 7 (1): 61-72. https://doi.org/10.1159/000014529
  • Hill SM, Frasch T, Xiang S, Yuan L, Duplessis T, Mao L. Molecular mechanisms of melatonin anticancer effects. Integrative cancer therapies. 2009; 8 (4): 337-346. https://doi.org/10.1177/1534735409353332
  • Cos S, Martínez-Campa C, Mediavilla MD, Sánchez-Barceló EJ. Melatonin modulates aromatase activity in MCF-7 human breast cancer cells. Journal of pineal research. 2005; 38 (2): 136-142. https://doi.org/10.1111/j.1600- 079X.2004.00186.x
  • Chottanapund S, Van Duursen MBM, Navasumrit P, Hunsonti P, Timtavorn S, Ruchirawat M, Berg MVd. Anti- aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts. Toxicology in vitro: an international journal published in association with BIBRA. 2014; 28 (7): 1215-1221. https://doi.org/10.1016/j.tiv.2014.05.015
  • Martínez-Campa C, González A, Mediavilla MD, Alonso-Gonzalez C, Alvarez-Garcia V, Sanchez-Barcelo EJ, Cos S. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells. British journal of cancer. 2009; 101 (9): 1613-1619. https://doi.org/10.1038/sj.bjc.6605336
  • Grigg-Damberger MM, Ianakieva D. Poor quality control of over-the-counter melatonin: what they say is often not what you get. Journal of clinical sleep medicine: JCSM : official publication of the American Academy of Sleep Medicine. 2017; 13 (2): 163. https://doi.org/10.5664/jcsm.6434
  • Rajaratnam SMW, Cohen DA, Rogers NL. Melatonin and melatonin analogues. Sleep Medicine Clincs. 2009; 4 (2): 179-193. https://doi.org/10.1016/j.jsmc.2009.02.007
  • Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica; the fate of foreign compounds in biological systems. 2019; 49 (5): 549-556. https://doi.org/10.1080/00498254.2018.1482029
  • Gurer-Orhan H, Suzen S. Melatonin, its metabolites and its synthetic analogs as multi-faceted compounds: antioxidant, prooxidant and ınhibitor of bioactivation reactions. Current medicinal chemistry. 2015; 22 (4): 490-499. http://doi.org/10.2174/0929867321666141215095259
  • Shirinzadeh H, Neuhaus E, Ince-Erguc E, Tascioglu-Aliyev A, Gurer-Orhan H, Suzen S. New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorganic chemistry. 2020; 104219. https://doi.org/10.1016/j.bioorg.2020.104219
  • Sanderson JT. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicological sciences: an official journal of the Society of Toxicology. 2006; 94 (1): 3-21. https://doi.org/10.1093/toxsci/kfl051
  • OECD Test No. 456: H295R Steroidogenesis Assay. https://read.oecd-ilibrary.org/environment/test-no-456-h295r- steroidogenesis-assay_9789264122642-en#page1. (accessed April 29, 2022).
  • Albert O, Desdoits-Lethimonier C, Lesné L, Legrand A, Guille F, Bensalah K, Dejucq-Rainsford N, Jegou B. Paracetamol, aspirin and indomethacin display endocrine disrupting properties in the adult human testis in vitro. Human reproduction (Oxford, England). 2013; 28 (7): 1890-1898. https://doi.org/10.1093/humrep/det112
  • Stukenborg JB, Mitchell RT, Söder O. Endocrine disruptors and the male reproductive system. Clinical endocrinology & metabolism. 2021; 35 (5), 101567. https://doi.org/10.1016/j.beem.2021.101567
  • Craig ZR, Wang W, Flaws JA. Endocrine-disrupting chemicals in ovarian function: Effects on steroidogenesis, metabolism and nuclear receptor signaling. Reproduction (Cambridge, England). 2011; 142: 633-646. https://doi.org/10.1530/REP-11-0136
  • Nielsen FK, Hansen CH, Fey JA, Hansen M, Jacobsen NW, Halling-Sorensen B, Björklund E, Styrishave B. H295R cells as a model for steroidogenic disruption: A broader perspective using simultaneous chemical analysis of 7 key steroid hormones. Toxicology in vitro: an international journal published in association with BIBRA. 2012; 26 (2): 343- 350. https://doi.org/10.1016/j.tiv.2011.12.008
  • OECD Work Related to Endocrine Disrupters. https://www.oecd.org/chemicalsafety/testing/oecdworkrelatedtoendocrinedisrupters.htm (accessed April 29, 2022).
  • Haggard DE, Karmaus AL, Martin MT, Judson RS, Setzer RW, Friedman KP. High-Throughput H295R Steroidogenesis Assay: Utility as an Alternative and a Statistical Approach to Characterize Effects on Steroidogenesis. Toxicological sciences: an official journal of the Society of Toxicology. 2018; 162 (2): 509-534. https://doi.org/10.1093/toxsci/kfx274
  • ATCC. NCI-H295R. https://www.atcc.org/products/crl-2128 (accessed June 15, 2022).
  • Higley EB, Newsted JL, Zhang X, Giesy JP, Hecker M. Assessment of chemical effects on aromatase activity using the H295R cell line. Environmental science and pollution research international. 2010; 17 (5): 1137-1148. https://doi.org/10.1007/s11356-009-0285-3
  • Hecker M, Giesy JP. Novel trends in endocrine disruptor testing: The H295R Steroidogenesis Assay for identification of inducers and inhibitors of hormone production. Analytical and bioanalytical chemistry. 2008; 390 (1): 287-291. https://doi.org/10.1007/s00216-007-1657-5
  • Maglich JM, Kuhn M, Chapin RE, Pletcher MT. More than just hormones: H295R cells as predictors of reproductive toxicity. Reproductive toxicology. 2014; 45: 77-86. https://doi.org/10.1016/j.reprotox.2013.12.009
  • Chase JE, Gidal BE. Melatonin: Therapeutic use in sleep disorders. The Annals of pharmacotherapy. 1997; 31 (10): 1218-1226. https://doi.org/10.1177/106002809703101015
  • Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Mühlbauer E. Melatonin and type 2 diabetes – a possible link?. Journal of pineal research. 2007; 42 (4): 350-358. https://doi.org/10.1111/j.1600-079X.2007.00426.x
  • Kiefer T, Ram PT, Yuan L, Hill SM. Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells. Breast cancer research and treatment 2002; 71 (1): 37-45. https://doi.org/10.1023/A:1013301408464
  • Cos S, Fernandez R, Güezmez A, Sãnchez-Barcelo EJ. Influence of melatonin on ınvasive and metastatic properties of mcf-7 human breast cancer cells. Cancer research. 1998; 58 (19): 4383-4390.
  • Hill SM, Belancio VP, Dauchy RT, Xiang S, Brimer S, Mao L, Hauch A, Lundberg PW, Summers W, Yuan L, Frasch T, Blask DE. Melatonin: an inhibitor of breast cancer. Endocrine-related cancer. 2015; 22 (3): R183-R204. https://doi.org/10.1530/ERC-15-0030
  • Hecker M, Hollert H, Cooper R, Vingguard AM, Akahori Y, Murphy M, Nellemann C, Higley E, Newsted J, Laskey J, Buckalew A, Grund S, Maletz S, Giesy J, Timm G. The OECD validation program of the H295R steroidogenesis assay: Phase 3. Final inter-laboratory validation study. Environmental science and pollution research international. 2018; 25 (15), 15265. https://doi.org/10.1007/s11356-010-0396-x
  • Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C. Melatonin: pharmacology, functions and therapeutic benefits. Current neuropharmacology. 2017; 15 (3): 434. http://doi.org/10.2174/1570159X14666161228122115
  • Darbre PD. Endocrine Disruption and Human Health. 1st ed, Reading, UK 2015. L
  • agarde F, Beausoleil C, Belcher SM, Belzunces LP, Emond C, Guerbet M, Rousselle C. Non-monotonic dose-response relationships and endocrine disruptors: A qualitative method of assessment. Environmental health: a global access science source. 2015; 14 (1): 1-15. http://doi.org/10.1186/1476-069X-14-13
  • Kaur K, Jaitak V. Recent Development in Indole Derivatives as Anticancer Agents for Breast Cancer. Anticancer Agents Med Chem. 2019;19(8):962-983. http://doi.org/10.2174/1871520619666190312125602
  • Sidhu JS, Singla R, Mayank, Jaitak V. Indole Derivatives as Anticancer Agents for Breast Cancer Therapy: A Review. Anticancer Agents Med Chem. 2015;16(2):160-73. http://doi.org/10.2174/1871520615666150520144217
  • Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica. 2019 May;49(5):549-556. https://doi.org/10.1080/00498254.2018.1482029
  • Shirinzadeh H, Neuhaus E, Ince-Erguc E, Tascioglu-Aliyev A, Gurer-Orhan H, Suzen S. New indole-7-aldehyde derivatives as melatonin analogues; synthesis and screening their antioxidant and anticancer potential. Bioorg Chem. 2020 Nov;104:104219. https://doi.org/10.1016/j.bioorg.2020.104219
  • Shirinzadeh H, Ince E, Westwell AD, Gurer-Orhan H, Suzen S. Novel indole-based melatonin analogues substituted with triazole, thiadiazole and carbothioamides: studies on their antioxidant, chemopreventive and cytotoxic activities. J Enzyme Inhib Med Chem. 2016 Dec;31(6):1312-21. https://doi.org/10.3109/14756366.2015.1132209
  • Öztürk-Ceylan Ö, MSc Thesis. Synthesis and biological activitie evaluation of new antimicrobial indole derivatives. Department of Biotechnology, Enstitute of Biotechnology, Ankara University, Keçiören, Ankara, Turkey, 2015.
Toplam 42 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Toksikoloji
Bölüm Articles
Yazarlar

Zeynep Ağlamış 0000-0002-2310-6321

Nil Bita Entezari Ökeer 0000-0003-1496-1091

Sibel Süzen 0000-0003-3413-6152

Hande Gürer-orhan 0000-0002-4890-299X

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 2

Kaynak Göster

APA Ağlamış, Z., Entezari Ökeer, N. B., Süzen, S., Gürer-orhan, H. (2025). The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. Journal of Research in Pharmacy, 27(2), 936-947.
AMA Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. Haziran 2025;27(2):936-947.
Chicago Ağlamış, Zeynep, Nil Bita Entezari Ökeer, Sibel Süzen, ve Hande Gürer-orhan. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy 27, sy. 2 (Haziran 2025): 936-47.
EndNote Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H (01 Haziran 2025) The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. Journal of Research in Pharmacy 27 2 936–947.
IEEE Z. Ağlamış, N. B. Entezari Ökeer, S. Süzen, ve H. Gürer-orhan, “The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect”, J. Res. Pharm., c. 27, sy. 2, ss. 936–947, 2025.
ISNAD Ağlamış, Zeynep vd. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy 27/2 (Haziran 2025), 936-947.
JAMA Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. 2025;27:936–947.
MLA Ağlamış, Zeynep vd. “The Effects of Melatonin and Its Analogues on Steroidogenesis Pathway: A Possible Therapeutical or Adverse Effect”. Journal of Research in Pharmacy, c. 27, sy. 2, 2025, ss. 936-47.
Vancouver Ağlamış Z, Entezari Ökeer NB, Süzen S, Gürer-orhan H. The effects of melatonin and its analogues on steroidogenesis pathway: a possible therapeutical or adverse effect. J. Res. Pharm. 2025;27(2):936-47.