Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era.

Peptides are at the cutting edge of contemporary research for new potent, selective, and safe therapeutical agents. Their rise has reshaped the pharmaceutical landscape, providing solutions to challenges that traditional small molecules often cannot address. A wide variety of natural and modified peptides have been obtained and studied, and many others are advancing in clinical trials, covering multiple therapeutic areas. As the demand for peptide-based therapies grows, so does the need for sustainable and environmentally friendly synthesis methods. Traditional peptide synthesis, while effective, often involves environmentally draining processes, generating significant waste and consuming vast resources. The integration of green chemistry offers sustainable alternatives, prioritizing eco-friendly processes, waste reduction, and energy conservation. This review delves into the transformative potential of applying green chemistry principles to peptide synthesis by discussing relevant examples of the application of such approaches to the production of active pharmaceutical ingredients (APIs) with a peptide structure and how these efforts are critical for an effective green transition era in the pharmaceutical field.

Jellyfish from Fisheries By-Catches as a Sustainable Source of High-Value Compounds with Biotechnological Applications.

The world's population growth and consequent increased demand for food, energy and materials together with the decrease of some natural resources have highlighted the compelling need to use sustainably existing resources and find alternative sources to satisfy the needs of growing and longer-aging populations. In this review, we explore the potential use of a specific fisheries by-catch, jellyfish, as a sustainable source of high-value compounds. Jellyfish are often caught up with fish into fishing gear and nets, then sorted and discarded. Conversely, we suggest that this by-catch may be used to obtain food, nutraceutical products, collagen, toxins and fluorescent compounds to be used for biomedical applications and mucus for biomaterials. These applications are based on studies which indicate the feasibility of using jellyfish for biotechnology. Because jellyfish exhibit seasonal fluctuations in abundance, jellyfish by-catches likely follow the same pattern. Therefore, this resource may not be constantly available throughout the year, so the exploitation of the variable abundances needs to be optimized. Despite the lack of data about jellyfish by-catches, the high value of their compounds and their wide range of applications suggest that jellyfish by-catches are a resource which is discarded at present, but needs to be re-evaluated for exploitation within the context of a circular economy in the era of zero waste.

Synthesis, anticancer and antioxidant properties of new indole and pyranoindole derivatives.

The indole scaffold has been recognized, over the years, as a model for the synthesis of compounds with anticancer activity by dint of its substantiated ability to act via multiple mechanisms, which also involves the inhibition of enzymes engaged in DNA replication. In this regard, a new series of indole and pyranoindole derivatives have been prepared, some of which showed good antitumor activity and proved their inhibitory effects on the tubulin target. The anticancer activity of the newly synthesized compounds has been evaluated on breast cancer cell lines, as MCF-7 and MDA-MB231, cervical cancer cells line HeLa and Ishikawa endometrial cancer cell line. Among the compounds under study, 7 exhibited a good antitumor activity on HeLa cell line (IC50 = 3.6 ± 0.5), leading to cell death by apoptosis due to the inhibition of tubulin polymerization, which demonstrated that the compound can explicate its function in a similar way to Vinblastine, a well-known inhibitor of tubulin polymerization. The data were also confirmed by in silico assays. No cytotoxicity against normal cells has been detected. Furthermore, in order to investigate the antioxidant properties, DPPH and ABTS tests were performed, together with fluorescence assays on 3T3-L1 cells. All our findings taken together led us to consider compound 7 a favourable candidate for the battle against cancer.

Utilization of Crab Waste for Cost-Effective Bioproduction of Prodigiosin.

This study aimed to establish the culture process for the cost-effective production of prodigiosin (PG) from demineralized crab shell powder (de-CSP), a fishery processing byproduct created via fermentation. Among the tested PG-producing strains, Serratia marcescens TNU02 was demonstrated to be the most active strain. Various ratios of protein/de-CSP were used as the sources of C/N for PG biosynthesis. The PG yield was significantly enhanced when the casein/de-CSP ratio was controlled in the range of 3/7 to 4/6. TNU02 produced PG with a high yield (5100 mg/L) in a 15 L bioreactor system containing 4.5 L of a newly-designed liquid medium containing 1.6% C/N source (protein/de-CSP ratio of 3/7), 0.02% (NH4)2SO4, 0.1% K2HPO4, and an initial pH of 6.15, at 27 °C for 8 h in dark conditions. The red pigment was purified from the culture broth and then quantified as being PG by specific Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and UV spectra analysis. The purified PG demonstrated moderate antioxidant and effective inhibition against four cancerous cell lines. Notably, this study was the first to report on using crab wastes for PG bioproduction with high-level productivity (5100 mg/L) in a large scale (4.5 L per pilot) in a short period of fermentation time (8 h). The salt compositions, including (NH4)2SO4 and K2HPO4, were also a novel finding for the enhancement of PG yield by S. marcescens in this report.

Berberine Derivatives Suppress Cellular Proliferation and Tumorigenesis In Vitro in Human Non-Small-Cell Lung Cancer Cells.

Lung cancer is the leading cause of death in the world, and the most common type of lung cancer is non-small-cell lung cancer (NSCLC), accounting for 85% of lung cancer. Patients with NSCLC, when detected, are mostly in a metastatic stage, and over half of patients diagnosed with NSCLC die within one year after diagnosis; the 5-year survival rate is 24%. However, in patients with metastatic NSCLC, the 5-year survival rate is 6%. Therefore, development of a new therapeutic agent or strategy is urgent for NSCLCs. Berberine has been illustrated to be a therapeutic agent of NSCLC. In the present study, we synthesized six derivatives of berberine, and the anti-NSCLC activity of these agents was examined. Some of them exert increasing proliferation inhibition comparing with berberine. Further studies demonstrated that two of the most effective agents, 9-O-decylberberrubine bromide (B6) and 9-O-dodecylberberrubine bromide (B7), performed cell cycle regulation, in-vitro tumorigenesis inhibition and autophagic flux blocking, but not induction of cellular apoptosis in NSCLC cells. Moreover, B6 and B7 were determined to be green fluorescent and could be penetrated and localized in cellular mitochondria. Herein, B6 and B7, the berberine derivatives we synthesized, revealed better anti-NSCLC activity with berberine and may be used as therapeutic candidates for the treatment of NSCLCs.

Novel tetrahydroisoquinolines as DHFR and CDK2 inhibitors: synthesis, characterization, anticancer activity and antioxidant properties.

In this study, we synthesized new 5,6,7,8-tetrahydroisoquinolines and 6,7,8,9-tetrahydrothieno[2,3-c]isoquinolines based on 4-(N,N-dimethylamino)phenyl moiety as expected anticancer and/or antioxidant agents. The structure of all synthesized compounds were confirmed by spectral date (FT-IR, 1H NMR, 13C NMR) and elemental analysis. We evaluated the anticancer activity of these compounds toward two cell lines: A459 cell line (lung cancer cells) and MCF7 cell line (breast cancer cells). All tested compounds showed moderate to strong anti-cancer activity towards the two cell lines. Compound 7e exhibited the most potent cytotoxic activity against A549 cell line (IC50: 0.155 µM) while compound 8d showed the most potent one against MCF7 cell line (IC50: 0.170 µM) in comparison with doxorubicin. In addition, we examined the effect of compounds 7e and 8d regarding the growth of A549 and MCF7 cell lines, employing flow cytometry and Annexin V-FITC apoptotic assay. Our results showed that compound 7e caused cell cycle arrest at the G2/M phase with a 79-fold increase in apoptosis of A459 cell line. Moreover, compound 8d caused cell cycle arrest at the S phase with a 69-fold increase in apoptosis of MCF7 cell line. Furthermore, we studied the activity of these compounds as enzyme inhibitors against several enzymes. Our findings by docking and experimental studies that compound 7e is a potent CDK2 inhibitor with IC50 of 0.149 µM, compared to the Roscovitine control drug with IC50 of 0.380 µM. We also found that compound 8d is a significant DHFR inhibitor with an IC50 of 0.199 µM, compared to Methotrexate control drug with IC50 of 0.131 µM. Evaluation of the antioxidant properties of ten compounds was also studied in comparison with Vitamin C. Compounds 1, 3, 6, 7c and 8e have higher antioxidant activity than Vitamin C which mean that these compounds can used as potent antioxidant drugs.

Benzothiazole-Phthalimide Hybrids as Anti-Breast Cancer and Antimicrobial Agents.

The benzothiazole nucleus is a major heterocyclic scaffold whose therapeutic potential has been thoroughly explored due to its structural simplicity and ease of synthesis. In fact, several benzothiazole derivatives have been synthesized over time, demonstrating numerous pharmacological properties such as anticancer, antimicrobial, anti-inflammatory, and antioxidant activities. Herein, we propose a new series of benzothiazole-phthalimide hybrids obtained by linking the phthalimide moiety to differently substituted benzothiazole nuclei through the N atom. These compounds have been screened for their anticancer properties against two human breast cancer cell lines. Furthermore, we delved into the mechanism of action of the most active hybrid, compound 3h, by assessing its capability to damage the nuclear DNA, trigger the apoptotic process in the high metastatic MDA-MB-231 cells, and prevent cellular migration. Moreover, in view of the documented antimicrobial activities of the two scaffolds involved, we explored the antibacterial and antifungal effects of the studied compounds by means of the broth microdilution method. Among the studied compounds, 3h showed the highest antimicrobial activity, both against gram-positive and gram-negative bacterial strains belonging to the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and against fungal strains of the Candida species with MICs values ranging from 16 to 32 µg/mL.

Adherence to oral anticancer therapy of oncology patients attending the pharmaceutical office of a public hospital in the lower Amazon region.

Introduction: Oral anticancer therapy has the benefit of allowing cancer patients to carry out their treatment at home, without being inconvenienced or being at risk of nosocomial infection. However, non-adherence is a public health problem that contributes to the clinical decline of the patient and there are no studies submitted on the adherence of cancer patients to oral anti-anticancer agents in Santarém, PA. Objective: In view of this, the general objective of this work was to evaluate this oral medication adherence. Methods: The methodology consisted of a cross-sectional documentary study with a quantitative approach of patients seen at the pharmaceutical office. The Morisky-Green test was used to analyse the degree of adherence and descriptive and inferential statistics were used (p < 0.05). Results: Patients' adherence to antitumour therapy was not 100%, the majority belonging to females; men were the most adherent, showing adverse reactions to anti-anticancer agents (p = 0.0096); comorbidity (p = 0.0202) negatively impacted adherence. Conclusion: It is necessary to adopt new clinical procedures that can contribute to the management of these variables that prevent adherence, in order to improve the effectiveness of the treatment of these patients. There are circumstances that go beyond the aspects inherent to the patient, so it is also relevant to research the external factors that influence the individual's behaviour, such as the duration of therapy and the consequences of the treatment in the patient's routine.