Novel sulfonamide-based compounds as dual inhibitors of hCYP1B1 and hCYP19A1 with anticancer activity against breast cancer cells DOI Open Access

Elif İnce,

Pınar Eraslan‐Elma, Atilla Akdemir

et al.

Journal of Research in Pharmacy, Journal Year: 2024, Volume and Issue: 29(3), P. 1098 - 1110

Published: Nov. 23, 2024

Cancer remains a critical global health challenge, driven by multifactorial etiologies, including oxidative stress, hormonal imbalances, and procarcinogen bioactivation. The cytochrome P450 enzymes CYP1B1 CYP19A1 play significant roles in these processes, with involved the bioactivation of carcinogens such as DMBA estrogens, being crucial estrogen biosynthesis, particularly hormone-dependent cancers. In this study, we synthesized novel sulfonamide-based 2-indolinone compound (7h) evaluated its inhibitory activity against human enzymes, along previously reported 1H-indole-2,3-dione 3-[4-(3- sulfamoylphenyl)thiosemicarbazones] (compounds 7-9). Additionally, cytotoxic effects compounds were tested on MCF-7 breast cancer cell line. R2 trifluoromethoxy-substituted 7c emerged most potent inhibitor both hCYP1B1 (IC50 = 0.97 μM) hCYP19A1 6.46 demonstrated cytotoxicity, reducing viability to below 70% at 10 μM. R1 methyl- substituted 7b, dimethyl- 8b ethyl- 9a reduced 60% after 24 hours incubation Molecular docking studies revealed key interactions between enzyme active sites, correlating their potency. These findings suggest that 2- indolinone derivatives, 7c, hold promise dual inhibitors CYP19A1, offering potential therapeutic benefits treatment other Further are warranted explore full clinical potential.

Language: Английский

In vitro Evaluation of Endocrine‐Related Adverse Effects of 5‐Fluoroindole Derived Melatonin Analogues with Antioxidant Activity DOI Open Access
Elif Ince Ergüç, Hanifa Fatullayev,

Bita Entezari

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Melatonin (MLT) is a natural indolic hormone with well documented antioxidant properties, but it can also modulate the estrogen signaling pathway by inhibiting aromatase enzyme and receptor modulating activity. This dual activity raises concerns about potential endocrine-related adverse effects when using MLT its analogues as therapeutic agents in prevention treatment of oxidative stress related diseases. In this study, 34 novel 5-fluoroindole derivatives were synthesized evaluated for their antioxidant, modulatory, inhibitory activities.Three compounds (4c, 5c, 6c) demonstrated significant activity, compound 4c showing highest efficacy reducing intracellular reactive oxygen species (ROS) 65 % CHO-K1 cells displaying DPPH radical scavenging comparable to standard BHT. However, these same exhibited antiestrogenic E-Screen assay, IC

Language: Английский

Citations

1
In Silico Discovery of Multi-Target Natural Ligands and Efficient siRNA Design for Overcoming Drug Resistance in Breast Cancer via Local Therapy DOI Open Access

Seyed Mohammad Javad Hashemi,

Ali Barzegar, Javad Akhtari

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract In this study, we designed an efficient siRNA for PKMYT1 gene knockdown, and evaluated the binding affinities of different natural ligands to crucial proteins involved in breast cancer. Designed showed strong affinity minimal off-target effects. Molecular docking studies identified new as antagonists with high aromatase, estrogen receptor alpha, HER2, PARP10, well agonists MT2 STING. The ligand SCHEMBL7562664 was introduced a golden due its among multiple targets lack cytotoxic mutagenic Natural small molecules research, their multi-target characteristics, provided solution overcome problem drug resistance cancer cells. Furthermore, proposed three dimensional scaffold design local therapy offers promising approach increase delivery efficacy these molecules, reduce systemic side effects, improve treatment outcomes. significant favorable pharmacokinetic properties were identified, which paves way further research targeted

Language: Английский

Citations

0
Further transformation of fungal catalyzed transformed metabolite 11β-hydroxy-dianabol into new aromatase inhibitors DOI

Muhammad Aamer,

M. Atif,

Mahwish Siddiqui

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 154, P. 108025 - 108025

Published: Dec. 3, 2024

Language: Английский

Citations

0
From biosynthesis to therapeutics: A comprehensive review on varied functions of estrogen and selective estrogen receptor modulators DOI

Akrati Sant,

Imran Ahmad,

Sonika Bhatia

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1327, P. 141197 - 141197

Published: Dec. 30, 2024

Language: Английский

Citations

0
Novel sulfonamide-based compounds as dual inhibitors of hCYP1B1 and hCYP19A1 with anticancer activity against breast cancer cells DOI Open Access

Elif İnce,

Pınar Eraslan‐Elma, Atilla Akdemir

et al.

Journal of Research in Pharmacy, Journal Year: 2024, Volume and Issue: 29(3), P. 1098 - 1110

Published: Nov. 23, 2024

Cancer remains a critical global health challenge, driven by multifactorial etiologies, including oxidative stress, hormonal imbalances, and procarcinogen bioactivation. The cytochrome P450 enzymes CYP1B1 CYP19A1 play significant roles in these processes, with involved the bioactivation of carcinogens such as DMBA estrogens, being crucial estrogen biosynthesis, particularly hormone-dependent cancers. In this study, we synthesized novel sulfonamide-based 2-indolinone compound (7h) evaluated its inhibitory activity against human enzymes, along previously reported 1H-indole-2,3-dione 3-[4-(3- sulfamoylphenyl)thiosemicarbazones] (compounds 7-9). Additionally, cytotoxic effects compounds were tested on MCF-7 breast cancer cell line. R2 trifluoromethoxy-substituted 7c emerged most potent inhibitor both hCYP1B1 (IC50 = 0.97 μM) hCYP19A1 6.46 demonstrated cytotoxicity, reducing viability to below 70% at 10 μM. R1 methyl- substituted 7b, dimethyl- 8b ethyl- 9a reduced 60% after 24 hours incubation Molecular docking studies revealed key interactions between enzyme active sites, correlating their potency. These findings suggest that 2- indolinone derivatives, 7c, hold promise dual inhibitors CYP19A1, offering potential therapeutic benefits treatment other Further are warranted explore full clinical potential.

Language: Английский

Citations

0