Smartphone-based application and nurses' interventions for symptoms monitoring in patients treated with oral anticancer agents: A 1-year follow-up in a tertiary cancer center.

AIM: The increasing use of oral anticancer agents over the past years has necessitated changes in monitoring toxicities to ensure patients' adherence and tolerance at home. The aim of this study was to describe nurses' interventions and medical changes after alerts triggered by a web-based platform designed to support the management of oral anticancer agents-related toxicities. METHODS: This retrospective study included patients undergoing oral anticancer agents in a cancer center from September 2018 to September 2019 (excluding hormonal therapy). In this cancer center, the standard of care included symptoms' collections for 1 month thanks to a web platform based on patient-reported outcomes. Patients had to fill a weekly questionnaire (Q1 to Q4). The web-based platform triggered orange alerts when patients reported moderate symptoms and red alerts when severe toxicities were declared. The rate of orange and red alerts, the rate of patients with medical changes consecutively to an orange or a red alert, and the different types of nurses' interventions and medical changes were assessed. RESULTS: A total of 524 patients were extracted but the final number of 436 patients were included in this study and 1488 questionnaires were filled in. More than 90% of patients declared that they took their medication as prescribed. Up to 60% of patients recorded all grade symptoms, including 8% of patients who recorded Grades 3-4 symptoms during the month, mostly anorexia, fatigue, and diarrhea. The web platform system triggered 700 orange and 212 red alerts: 305/700 (44%) of orange alerts resulted in nurses' interventions, most frequently phone counseling (78%), and 65/212 (31%) of red alerts resulted in medical changes, most frequent treatment interruptions (48%). CONCLUSION: Implementing an e-health (electronic-health) system can be helpful for monitoring symptoms in patients under oral anticancer agents, enhancing that this organization should be a standard of care in every cancer centers.

Synthesis and antimicrobial activity of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines.

A series of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines (1) and (2) were synthesized and evaluated for their antimicrobial activity against three representative gram-positive bacteria and two fungi. The structure-activity relationship (SAR) demonstrates that the 3- or 4-fluorophenyl component attached directly to the triazine ring was essential for activity. Of these compounds, 14, 15, and 25 demonstrated significant activity against all selected organisms compared to control. These compounds were generally nontoxic and may prove useful as antimicrobial agents.

Design and Synthesis of New 1,3,5-Trisubstituted Triazines for the Treatment of Cancer and Inflammation.

Low-molecular-weight synthetic molecules 1 with the general 2-(fluorophenylamino)-4,6-disubstituted 1,3,5-triazine structure and showing anti-inflammatory and anticancer activities were explored. Structure-activity relationship studies demonstrated the importance of the aminopentyl chain, the 3- or 4-fluorophenylaniline component, and the presence of at least one substituent, such as a tyramine moiety, attached directly to the triazine ring as essential for good activity. These compounds, represented by leads 4-{2-[4-(5-Aminopentylamino)-6-(3-fluorophenylamino)-1,3,5-triazin-2-ylamino]ethyl}phenol (6) and 4-{2-[4-(5-Aminopentylamino)-6-(4-fluorophenylamino)-1,3,5-triazin-2-ylamino]ethyl}phenol (10), displayed moderate and significant in vitro and in vivo dual activities, respectively, and address the molecular link between inflammation and cancer. Compound 10 demonstrated significant antitumor efficacy upon administration by the oral and intravenous routes in several animal models. This class of triazine compounds is new, safe, and nontoxic and offers a novel approach to the treatment of inflammation and cancer.

Synthesis of unique 17beta-estradiol homo-dimers, estrogen receptors binding affinity evaluation and cytocidal activity on breast, intestinal and skin cancer cell lines.

A rapid and efficient synthesis of a series of C2-symmetric 17beta-estradiol homo-dimers is described. The new molecules are linked at position 17alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in only five chemical steps with an overall yield exceeding 30%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER+ and ER-) human breast tumor cell lines: MCF-7 and MDA-MB-231. Some of the dimers present selective cytotoxic activity against the ER+ cell line. However, they are not very cytotoxic when compared to the antiestrogen tamoxifen. Unfortunately, they show only weak affinity for the estrogen receptor alpha (ERalpha) and no affinity for the estrogen receptor beta (ERbeta). The new compounds were also tested on human intestinal (HT-29) cancer and on murine skin cancer (B16-F10) cell lines for further biological assessment. Interestingly, the dimers were found to be cytotoxic to the murine skin cancer cell line but were inactive towards the intestinal cancer cell line.

2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases.

A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.

Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-acyl aromatic alpha-amino acids.

A series of lysine sulfonamide analogues bearing Nepsilon-acyl aromatic amino acids were synthesized using an efficient synthetic route. Evaluation of these novel protease inhibitors revealed compounds with high potency against wild-type and multiple-protease inhibitor-resistant HIV viruses.

Synthesis of 17beta-estradiol-linked platinum(II) complexes and their cytocidal activity on estrogen-dependent and -independent breast tumor cells.

The synthesis of two new highly potent 17beta-estradiol-linked platinum(II) complexes is described. The new molecules are linked at position 16 of the steroid nucleus with an alkyl chain. They are made from estrone in nine chemical steps with an overall yield exceeding 10%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. The novel compounds prove to be highly cytotoxic against breast cancer cell lines. The most cytotoxic derivative shows high affinity for the estrogen receptor alpha.

A facile synthesis of C(2)-symmetric 17 beta-estradiol dimers.

A rapid and efficient synthesis of a series of C(2)-symmetric 17 beta-estradiol dimers is described. The new molecules are linked at position 17 alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in five chemical steps with an overall yield exceeding 30%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. Some of the dimers present selective cytotoxic activity against the ER(+) cell line.

Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-disubstituted ureas.

A series of lysine sulfonamide analogues bearing a Nepsilon-benzylic ureas was synthesized using both solution-phase and solid-phase approaches. A novel synthetic route of Nalpha-(alkyl)-Nalpha-(sulfonamides)lysinol using alpha-amino-caprolactam was developed. Evaluation of these novel protease inhibitors revealed compounds with high potency against wild-type HIV virus.

Synthesis of 17beta-estradiol platinum(II) complexes: biological evaluation on breast cancer cell lines.

The synthesis of a novel series of 17beta-estradiol-linked platinum(II) complexes is described. The new molecules are linked with an alkyl chain at position 16alpha of the steroid nucleus and bear a 16beta-hydroxymethyl side chain. They are made from estrone in five chemical steps with an overall yield exceeding 28%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER+ and ER-) human breast cancers. The derivatives incorporating a 2-(2'-aminoethyl)pyridine ligand displayed good activity against the cell lines particularly when the connecting arm is 10 carbon atoms long.