ABSTRACT
Chalcones are chemical scaffolds found in natural products, particularly in plants, and are considered for structural diversity in medicinal chemistry for drug development. Herein, we designed and synthesised novel acetamide derivatives of chalcone, characterizing them using 1H NMR, 13C NMR, HRMS, and IR spectroscopic methods. These derivatives were then screened against human cancer cells for cytotoxicity using the SRB assay. Among the tested derivatives, 7g, with a pyrrolidine group, exhibited better cell growth inhibition activity against triple-negative breast cancer (TNBC) cells. Further assays, including SRB, colony formation, and fluorescent dye-based microscopic analysis, confirmed that 7g significantly inhibited MDA-MB-231 cell proliferation. Furthermore, 7g promoted apoptosis by upregulating cellular reactive oxygen species (ROS) levels and disrupting mitochondrial membrane potential (MMP). Elevated expression of pro-apoptotic proteins (Bax and caspase-3) and a higher Bax/Bcl-2 ratio with downregulation of anti-apoptotic (Bcl-2) protein levels were observed in TNBC cells. The above results suggest that 7g can promote cellular death through apoptotic mechanisms in TNBC cells.
Subject(s)
Acetamides , Antineoplastic Agents , Apoptosis , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Cell Proliferation/drug effects , Acetamides/pharmacology , Acetamides/chemical synthesis , Acetamides/chemistry , Apoptosis/drug effects , Molecular Structure , Cell Line, Tumor , Chalcones/pharmacology , Chalcones/chemistry , Chalcones/chemical synthesis , Dose-Response Relationship, Drug , Chalcone/pharmacology , Chalcone/chemistry , Chalcone/chemical synthesis , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effectsABSTRACT
PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.
Subject(s)
Fatty Acids, Omega-3/therapeutic use , Keratoconjunctivitis Sicca/drug therapy , gamma-Linolenic Acid/therapeutic use , Adult , Aged , Aged, 80 and over , CD11c Antigen/metabolism , Conjunctiva/physiology , Corneal Topography , Double-Blind Method , Fatty Acids, Omega-3/adverse effects , Female , Fluorescein/chemistry , HLA-DR Antigens/metabolism , Humans , Keratoconjunctivitis Sicca/metabolism , Lissamine Green Dyes/chemistry , Male , Middle Aged , Ophthalmic Solutions , Patient Compliance , Staining and Labeling/methods , Tears/physiology , Visual Acuity/physiology , gamma-Linolenic Acid/adverse effectsABSTRACT
AIM: To describe the long-term outcomes of lens-sparing vitrectomy (LSV) for retinopathy of prematurity (ROP). METHODS: Single-centre retrospective case series of eyes that underwent LSV for ROP between 1998 and 2005 and had a follow-up of at least 5 years. The primary outcome was the mean visual acuity, and secondary outcomes were the proportion of eyes without functional vision, proportion of eyes with anatomic success, proportion of Stage 4A eyes with vision better than 20/400, proportion of Stage 4B eyes with vision better than 20/800. RESULTS: Thirty-seven eyes of 30 patients (mean age at last follow-up: 7.1 years) were included in the study, while an additional 23 patients had been lost to follow-up and were not included in the study. Of eyes that underwent LSV for Stage 4A or 4B: 63% had measurable visual acuity (mean logMAR 0.92 for Stage 4A, 1.63 for Stage 4B), 19% had form vision, but neurological comorbidities precluded visual acuity measurement, and the remaining 18% had light perception or no light perception. CONCLUSIONS: While most eyes that underwent LSV for Stage 4A or 4B ROP maintain useful vision with long-term follow-up, approximately one-fifth of eyes had no functional vision, and in a further fifth, vision could not be measured due to severe neurological impairment.
Subject(s)
Lens, Crystalline/surgery , Retinopathy of Prematurity/surgery , Visual Acuity , Vitrectomy/methods , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Lens, Crystalline/physiopathology , Male , Retinopathy of Prematurity/physiopathology , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: To evaluate intraocular pressure (IOP) control and the ocular adverse effects resulting from a large-scale transition from latanoprost to travoprost among patients at a Veterans Affairs Medical Center (VAMC) Eye Clinic. METHODS: Retrospective chart review of patients transitioned from latanoprost to travoprost after a revision of the drug formulary used by the VAMC in Houston, Texas. IOP control after changing medications and the incidence of ocular adverse effects attributed to travoprost were the main outcomes measured. For patients who were using IOP-lowering medications bilaterally, the worse eye was used for all IOP analyses. Long-term retention in IOP control plus a cost-saving analysis were presented as a secondary assessment. RESULTS: Five hundred ninety-nine (599) patients with 1,041 treated eyes were evaluated. Mean IOP was 15.86 +/- 4.15 mmHg among patients using latanoprost prior to the prostaglandin analog transition. After transitioning to travoprost, the mean IOP was 15.78 +/- 4.38 mmHg. The mean within-eye change in IOP in the worse eye when transitioned from latanoprost to travoprost was -0.07 +/- 3.27 mmHg (P = 0.5914). Twenty-four (24) patients (4%) experienced an ocular adverse effect while using travoprost. In the long-term retention analysis at 1 year, mean change in IOP from the time of the original change to travoprost was +0.21 +/- 3.71 mmHg (P = 0.2683). CONCLUSIONS: The large-scale transition from latanoprost to travoprost maintained long-term IOP control. Only a small percentage of clinic patients experienced mild ocular adverse effects after being transitioned to the new prostaglandin analog.
