(E)-1-(3-(3-Hydroxy-4-Methoxyphenyl)-1-(3,4,5-Trimethoxyphenyl)allyl)-1H-1,2,4-Triazole and Related Compounds: Their Synthesis and Biological Evaluation as Novel Antimitotic Agents Targeting Breast Cancer

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 118 - 118

Published: Jan. 17, 2025

Background/Objectives: The synthesis of (E)-1-(1,3-diphenylallyl)-1H-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These were designed hybrids the microtubule-targeting chalcones, indanones, aromatase inhibitor letrozole. Methods: A panel 29 synthesized examined by a preliminary screening estrogen receptor (ER) progesterone (PR)-positive MCF-7 cells together cell cycle analysis tubulin polymerization inhibition. Results: (E)-5-(3-(1H-1,2,4-triazol-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2-methoxyphenol 22b identified potent antiproliferative compound an IC50 value 0.39 mM cells, 0.77 triple-negative MDA-MB-231 0.37 leukemia HL-60 cells. In addition, demonstrated sub-micromolar range against NCI 60 line including prostate, melanoma, colon, leukemia, non-small lung cancers. G2/M phase arrest induction apoptosis inhibition demonstrated. Immunofluorescence studies confirmed that targeted while computational docking predicted binding conformations for colchicine site tubulin. Compound also selectively inhibited aromatase. Conclusions: Based on results obtained, these novel are suitable candidates further investigation cancer.

Language: Английский

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Synthesis, Anti-proliferation, Apoptosis Induction in Breast Cancer Cells, and Aromatase Inhibition of Coumarin-Triazole Hybrids: In Vitro and In Silico Studies

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110308 - 110308

Published: Jan. 1, 2025

Language: Английский

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Design, Synthesis and Evaluation of Novel 1,3-Benzodioxole Derivatives for Their Anti-Tumor Activity

Published: Jan. 1, 2025

Language: Английский

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The current landscape of aromatase inhibitors for the treatment of estrogen receptor-positive breast carcinoma

The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2025, Volume and Issue: 250, P. 106729 - 106729

Published: March 7, 2025

Language: Английский

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Drug-Induced Liver Injury Secondary to Endocrine Therapy With Aromatase Inhibitors: A Case Report

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Aromatase inhibitors (AIs) are routinely used in treating estrogen receptor (ER)-positive breast cancer postmenopausal women and effective reducing the recurrence of metastatic hormone-sensitive cancer. We present case a 76-year-old female with past medical history hypothyroidism dyslipidemia who presented for treatment ER-positive pleomorphic lobular carcinoma situ (LCIS). After initiating anastrozole, she developed weakness, loss appetite, darkening urine, jaundice. Upon admission to hospital, results from patient's initial workup revealed abnormal liver function tests. Anastrozole was identified as causative agent hepatic injury discontinued. The enzymes normalized two months off medication, decided proceed routine observation rather than new endocrine therapy. This emphasizes importance recognizing drug-induced (DILI) rare serious complication anastrozole use highlights need consideration possible risks therapies.

Language: Английский

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Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 2, 2025

Steroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes steroidogenesis, thus reducing circulating levels relevant oestrogenic androgenic hormones responsible for cancer survival proliferation. Therefore, enzyme inhibition represents an intriguing endocrine approach treatment hormone-dependent tumours, such breast prostate cancer, with well-known approved drugs several pre-clinical clinical candidates under investigation. This review summarises advancements over past decade (2014-2024) development inhibitors endowed anticancer activity, illustrating their mechanisms action, potential, drug design approaches, current applications. Furthermore, we discuss challenges related resistance, off-target effects, future strategies optimise efficacy

Language: Английский

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Simulation, 3D-QSAR, molecular docking and pharmacophore mapping studies on indole derivatives as aromatase inhibitors

Letters in Drug Design & Discovery, Journal Year: 2025, Volume and Issue: unknown, P. 100007 - 100007

Published: April 1, 2025

Language: Английский

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Novel nonhormonal treatments for vasomotor symptoms of menopause

Current Opinion in Obstetrics & Gynecology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Purpose of review Hot flashes are a prevalent and bothersome symptom associated with menopause. Beyond the fact that they cause discomfort, hot responsible for significant healthcare costs lost productivity among midlife women. They may also be harbinger future disease risk. While hormone therapy is mainstay treatment, many women cannot or do not wish to take hormones mitigate their flashes. Recent findings The discovery linkage neurokinin (NK) receptor has resulted in rapid bench-to-bedside development new class compounds targeting NK3 its related pathways. Fezolinetant first FDA-approved medication this class, elinzanetant awaiting FDA approval. Both agents effective against represent exciting nonhormonal treatments free untoward off-target effects. have demonstrated improvements patient self-reported sleep outcomes. Summary Targeting NK hypothalamus led availability options menopausal suffering from

Language: Английский

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NSG2: a promising prognostic marker shaping the immune landscape of breast cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 18, 2024

Breast cancer (BC) remains a significant health issue globally and most common cause of mortality in women. Enhancing our understanding on biomarkers may greatly improve both diagnostic therapeutic approaches to this disease.

Language: Английский

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In vitro Evaluation of Endocrine‐Related Adverse Effects of 5‐Fluoroindole Derived Melatonin Analogues with Antioxidant Activity

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

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