The impact of biomolecule interactions on the cytotoxic effects of rhenium(I) tricarbonyl complexes.

Rhenium complexes show great promise as anticancer drug candidates. Specifically, compounds with a Re(CO)3(NN)(py)+ core in their architecture have shown cytotoxicity equal to or greater than that of well-established anticancer drugs based on platinum or organic molecules. This study aimed to evaluate how the strength of the interaction between rhenium(I) tricarbonyl complexes fac-[Re(CO)3(NN)(py)]+, NN = 1,10-phenanthroline (phen), dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or dipyrido[3,2-a:2'3'-c]phenazine (dppz) and biomolecules (protein, lipid and DNA) impacted the corresponding cytotoxic effect in cells. Results showed that fac-[Re(CO)3(dppz)(py)]+ has higher Log Po/w and binding constant (Kb) with biomolecules (protein, lipid and DNA) compared to complexes of fac-[Re(CO)3(phen)(py)]+ and fac-[Re(CO)3(dpq)(py)]+. As consequence, fac-[Re(CO)3(dppz)(py)]+ exhibited the highest cytotoxicity (IC50 = 8.5 µM for HeLa cells) for fac-[Re(CO)3(dppz)(py)]+ among the studied compounds (IC50 > 15 µM). This highest cytotoxicity of fac-[Re(CO)3(dppz)(py)]+ are probably related to its lipophilicity, higher permeation of the lipid bilayers of cells, and a more potent interaction of the dppz ligand with biomolecules (protein and DNA). Our findings open novel avenues for rational drug design and highlight the importance of considering the chemical structures of rhenium complexes that strongly interact with biomolecules (proteins, lipids, and DNA).

Anti-Inflammatory and Cytotoxic Compounds Isolated from Plants of Euphorbia Genus.

Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different Euphorbia species have anti-cancer activity. In this review, we included compounds isolated from species of the Euphorbia genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords Euphorbia with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the Euphorbia genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%).

Antioxidants from different citrus peels provide protection against cancer / Antioxidantes de diferentes cascas de frutas cítricas como agentes preventivos contra o câncer

Cancer is one of the leading causes of death. Despite significant advancements in the discovery of medications for the treatment of cancer, these drugs are hindered by applicability and efficacy issues and frequently exhibit major side effects that can further impair patients 'quality of life. Therefore, the development of therapeutically sound anti-cancer medicines derived from natural products has gained prominence in the field of functional foods. Some of these compounds have shown efficacy in the prevention and treatment of cancer as well as low toxicity. Additionally, many recent studies have explored the recycling of agro-industrial waste to create bioactive chemicals. Citrus peels are produced in vast quantities in the food processing sector; due to their abundance of flavonoids, they may be inexpensive sources of protection against several cancers. Citrus is a common type of fruit that contains a variety of nutrients. In particular, the antioxidant chemicals found in citrus peel have been identified as potential cancer-fighting agents. Antioxidant substances such as flavonoids prevent the development of cancer by inhibiting the metastatic cascade, decreasing the mobility of cancer cells in the circulatory system, promoting apoptosis, and suppressing angiogenesis. To explore the most effective uses of citrus peel-derived antioxidants, this review presents background information, an overview of the role of citrus antioxidants in cancer therapy, and a discussion of the key underlying molecular mechanisms.

O câncer é uma das principais causas de morte. Apesar dos avanços significativos na descoberta de medicamentos para o tratamento do câncer, esses medicamentos são prejudiciais por questões de aplicabilidade e eficácia e frequentemente apresentam efeitos colaterais importantes que podem afetar ainda mais a qualidade de vida dos pacientes. Portanto, o desenvolvimento de medicamentos anticancerígenos, terapeuticamente adequados derivados de produtos naturais, ganhou destaque no campo dos alimentos funcionais. Alguns desses compostos demonstraram eficácia na prevenção e tratamento do câncer, bem como baixa toxicidade. Além disso, muitos estudos recentes exploraram a reciclagem de resíduos agroindustriais para criar produtos químicos bioativos. As cascas de frutas cítricas são produzidas abundantemente no setor de processamento de alimentos; devido à abundância de flavonoides, e são fontes baratas de proteção contra várias categorias de câncer. Citrus é um tipo comum de fruta que contém uma variedade de nutrientes. Em particular, os produtos químicos antioxidantes encontrados na casca de frutas cítricas foram identificados como potenciais agentes de combate ao câncer. Substâncias antioxidantes, como os flavonoides, previnem o desenvolvimento do câncer, inibindo a cascata metastática, diminuindo a mobilidade das células cancerígenas no sistema circulatório, promovendo a apoptose e suprimindo a angiogênese. Para explorar os usos mais eficazes dos antioxidantes derivados da casca de frutas cítricas, esta revisão apresenta informações básicas, uma visão geral do papel dos antioxidantes cítricos na terapia do câncer e uma discussão dos principais mecanismos moleculares subjacentes.

Anticancer Potential of Flavonoids: An Overview with an Emphasis on Tangeretin.

Natural compounds with pharmacological activity, flavonoids have been the subject of an exponential increase in studies in the field of scientific research focused on therapeutic purposes due to their bioactive properties, such as antioxidant, anti-inflammatory, anti-aging, antibacterial, antiviral, neuroprotective, radioprotective, and antitumor activities. The biological potential of flavonoids, added to their bioavailability, cost-effectiveness, and minimal side effects, direct them as promising cytotoxic anticancer compounds in the optimization of therapies and the search for new drugs in the treatment of cancer, since some extensively antineoplastic therapeutic approaches have become less effective due to tumor resistance to drugs commonly used in chemotherapy. In this review, we emphasize the antitumor properties of tangeretin, a flavonoid found in citrus fruits that has shown activity against some hallmarks of cancer in several types of cancerous cell lines, such as antiproliferative, apoptotic, anti-inflammatory, anti-metastatic, anti-angiogenic, antioxidant, regulatory expression of tumor-suppressor genes, and epigenetic modulation.

A New Quinone-Based Inhibitor of Mitochondrial Complex I in D-Conformation, Producing Invasion Reduction and Sensitization to Venetoclax in Breast Cancer Cells.

Mitochondrial Complex I plays a crucial role in the proliferation, chemoresistance, and metastasis of breast cancer (BC) cells. This highlights it as an attractive target for anti-cancer drugs. Using submitochondrial particles, we identified FRV-1, an ortho-carbonyl quinone, which inhibits NADH:duroquinone activity in D-active conformation and reduces the 3ADP state respiration dependent on Complex I, causing mitochondrial depolarization, ATP drop, increased superoxide levels, and metabolic remodeling towards glycolysis in BC cells. Introducing methyl groups at FRV-1 structure produced analogs that acted as electron acceptors at the Complex I level or increased the inhibitory effect of FCCP-stimulated oxygen consumption rate, which correlated with their redox potential, but increased toxicity on RMF-621 human breast fibroblasts was observed. FRV-1 was inactive in the naphthoquinone oxidoreductase 1 (NOQ1)-positive BC cell line, MCF7, but the sensitivity was recovered by dicoumarol, a NOQ1 inhibitor, suggesting that FRV-1 is a NOQ1 substrate. Importantly, FRV-1 selectively inhibited the proliferation, migration, and invasion of NQO1 negative BC cell, MDA-MB-231, in an OXPHOS- and ROS-dependent manner and sensitized it to the BH3 mimetic drug venetoclax. Overall, FRV-1 is a novel Complex I inhibitor in D-active conformation, blocking possibly the re-activation to A-state, producing selective anti-cancer effects in NQO1-negative BC cell lines.

Calotropis procera (Aiton) Dryand (Apocynaceae): State of the art of its uses and Applications.

Calotropis procera (Aiton) Dryand (Apocynaceae), popularly known as milkweed, has been traditionally used to treat diseases particularly associated with gastric disorders, skin disease and inflammatory processes. The present study aimed to review the current scientific evidence regarding the pharmacological effects of C. procera extracted phytochemicals and possible research opportunities as complementary and alternative medicine. Scientific publications were searched in various electronic databases (PubMed, Scopus, Web of Science, Google Scholar, Springer, Wiley, and Mendeley) using the following search terms: Calotropis procera, medicinal plants, toxicity, phytochemical characterization, and biological effects. Collected data showed that cardenolides, steroid glycoside and flavonoids are the main classes of phytochemicals identified in C. procera latex and leaves. In addition, lignans, terpenes, coumarins, and phenolic acids have been reported. These metabolites have been correlated with their biological activities, including mainly antioxidant, anti-inflammatory, antitumoral, hypoglycemic, gastric protective, anti-microbial, insecticide, anti-fungal, anti-parasitic, among others. However, some of the studies were carried out with only a single dose or with a high dose not achievable under physiological conditions. Therefore, the validity of C. procera biological activity may be questionable. Not less important to highlight are the risks associated with its use and the possibility of accumulation of heavy metals that can be toxic. Furthermore, there are no clinical trials with C. procera to date. In conclusion, the need of bioassayguided isolation of bioactive compounds, bioavailability and efficacy, as well as pharmacological and toxicity studies, are needed using in vivo models and clinical trials in order to support the traditionally claimed health benefits.

Black rice and its by-products: anthocyanin-rich extracts and their biological potential.

Recently, growing demand for products enriched with natural compounds that support human health has been observed. Black rice, its by-products, and residues are known to have in their composition a large amount of these compounds with biological potential, mainly anthocyanins. These compounds have reported effects on anti-obesity, antidiabetic, antimicrobial, anticancer, neuroprotective, and cardiovascular disease. Therefore, the extract from black rice or its by-products have great potential for application as ingredients in functional foods, supplements, or pharmacological formulations. This overview summarizes the methods employed for the extraction of anthocyanins from both black rice and its by-products. In addition, trends in applications of these extracts are also evaluated regarding their biological potential. Commonly, the extraction methods used to recover anthocyanins are conventional (maceration) and some emerging technologies (Ultrasound-Assisted Extraction - UAE, and Microwave-Assisted Extraction - MAE). Anthocyanin-rich extracts from black rice have presented a biological potential for human health. In vitro and in vivo assays (in mice) showed these compounds mainly with anti-cancer properties. However, more clinical trials are still needed to prove these potential biological effects. Extracts from black rice and its by-products have great potential in applying functional products with beneficial characteristics to humans and reducing agro-industrial residues.

Synthesis and Cytotoxicity Studies of Br-Substituted Salphen Organic Compounds.

We present the synthesis and characterization of organic Salphen compounds containing bromine substituents at the para/ortho-para positions, in their symmetric and non-symmetric versions, and describe the X-ray structure and full characterization for the new unsymmetrical varieties. We report for the first time antiproliferative activity in metal-free brominated Salphen compounds, by evaluations in four human cancer cell lines, cervix (HeLa), prostate (PC-3), lung (A549) and colon (LS 180) and one non-cancerous counterpart (ARPE-19). We assessed in vitro cell viability against controls using the MTT assay ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)) and determined the concentration required for 50 % growth inhibition (IC50 ), together with their selectivity vs. non-cancerous cells. We found promising results against prostate (9.6 µM) and colon (13.5 µM) adenocarcinoma cells. We also found a tradeoff between selectivity (up to 3-fold vs. ARPE-19) and inhibition, depending upon the symmetry and bromine-substitution of the molecules, showing up to 20-fold higher selectivity vs. doxorubicin controls.

Rosmarinic acid decreases viability, inhibits migration and modulates expression of apoptosis-related CASP8/CASP3/NLRP3 genes in human metastatic melanoma cells.

Cutaneous melanoma is the most aggressive type of skin cancer; it is difficult to treat, and has been highlighted in recent years due to increasing numbers of cases worldwide. The use of antitumoral therapeutics for this neoplasm has been associated with severe side effects, low quality of life, and resistance. We aimed in this study to explore the effect of the phenolic compound rosmarinic acid (RA) on human metastatic melanoma cells. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of RA. In parallel, peripheral blood mononuclear cells (PBMCs) also were treated with RA under the same experimental conditions to verify the cytotoxic effect on non-tumoral cells. Then, we assessed cell viability and migration, levels of intracellular and extracellular reactive oxygen species (ROS), as well as nitric oxide (NOx), non-protein thiols (NPSH), and total thiol (PSH). Gene expression of the caspase 8, caspase 3 and NLRP3 inflammasome was evaluated by RT-qPCR. The enzymatic activity of the caspase 3 protein was assessed by a sensitive fluorescent assay. Fluorescence microscopy was employed to corroborate the effects of RA on melanoma cell viability, mitochondria transmembrane potential and apoptotic bodies formation. We found that RA potently reduces melanoma cell viability and migration after 24 h of treatment. On the other hand, it has no cytotoxic effect on non-tumoral cells. The fluorescence micrographics indicated that RA reduces transmembrane potential of mitochondria and induces apoptotic bodies formation. Moreover, RA significantly decreases intracellular and extracellular ROS levels, and increases the antioxidant defenders NPSH and PSH. A remarkable feature found in our study was that RA strongly upregulates the gene expression of the caspase 8 and caspase 3, and downregulates NLRP3 inflammasome expression. Similar to gene expression, RA greatly increases the enzymatic activity of caspase 3 protein. Taken together, we have shown for the first time that RA reduces cell viability and migration of human metastatic melanoma cells, in addition to modulates apoptosis-related gene expression. We suggest that RA may have the potential to be used in a therapeutic perspective, particularly for CM cell treatment.

Endostatin and Cancer Therapy: A Novel Potential Alternative to Anti-VEGF Monoclonal Antibodies.

Angiogenesis is a physiological process that consists of the formation of new blood vessels from preexisting ones. Angiogenesis helps in growth, development, and wound healing through the formation of granulation tissue. However, this physiological process has also been linked to tumor growth and metastasis formation. Indeed, angiogenesis has to be considered as a fundamental step to the evolution of benign tumors into malignant neoplasms. The main mediator of angiogenesis is vascular endothelial growth factor (VEGF), which is overexpressed in certain cancers. Thus, there are anti-VEGF monoclonal antibodies, such as bevacizumab, used as anti-cancer therapies. However, bevacizumab has shown adverse events, such as hypertension and proteinuria, which in the most severe cases can lead to cessation of therapy, thus contributing to worsening patients' prognosis. On the other hand, endostatin is an endogenous protein that strongly inhibits VEGF expression and angiogenesis and shows a better safety profile. Moreover, endostatin has already given promising results on small scale clinical studies. Hence, in this review, we present data supporting the use of endostatin as a replacement for anti-VEGF monoclonal antibodies.

Lithium: A Promising Anticancer Agent.

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and metastasis and cell cycle arrest. Moreover, lithium is synergistic with standard cancer therapies, enhancing their anti-tumor effects. In addition, lithium has a neuroprotective role in cancer patients, by improving their quality of life. Interestingly, nano-sized lithium enhances its anti-tumor activities and protects vital organs from the damage caused by lipid peroxidation during tumor development. However, these potential therapeutic activities of lithium depend on various factors, such as the nature and aggressiveness of the tumor, the type of lithium salt, and its form of administration and dosage. Since lithium has been used to treat bipolar disorder, the current study provides an overview of its role in medicine and how this has changed. This review also highlights the importance of this repurposed drug, which appears to have therapeutic cancer potential, and underlines its molecular mechanisms.

Use of Refractance Window Drying as an Alternative Method for Processing the Microalga Spirulina platensis.

Microalgae such as Spirulina platensis have recently attracted the interest of the pharmaceutical, nutritional and food industries due to their high levels of proteins and bioactive compounds. In this study, we investigated the use of refractance window (RW) drying as an alternative technology for processing the microalga Spirulina biomass aiming at its dehydration. In addition, we also analyzed the effects of operating variables (i.e., time and temperature) on the quality of the final product, expressed by the content of bioactive compounds (i.e., total phenolics, total flavonoids, and phycocyanin). The results showed that RW drying can generate a dehydrated product with a moisture content lower than 10.0%, minimal visual changes, and reduced process time. The content of bioactive compounds after RW drying was found to be satisfactory, with some of them close to those observed in the fresh microalga. The best results for total phenolic (TPC) and total flavonoids (TFC) content were obtained at temperatures of around 70 °C and processing times around 4.5 h. The phycocyanin content was negatively influenced by higher temperatures (higher than 80 °C) and high exposing drying times (higher than 4.5 h) due to its thermosensibility properties. The use of refractance window drying proved to be an interesting methodology for the processing and conservation of Spirulina platensis, as well as an important alternative to the industrial processing of this biomass.

Investigation of the female infertility risk associated with anti-cancer therapy.

Female infertility is a significant health issue worldwide with a rising incidence. Anti-cancer therapy is one of the most important reasons for increasing infertility. Although anti-cancer treatment increases the rate of survival, it decreases the quality of life through its side effects. The most substantial side effects are sexual dysfunction and infertility. Breast cancer is the most common cancer. The first-line treatment of breast cancer is chemotherapy by alkylating agents like cyclophosphamide, which leads to infertility. For instance, persistent chemotherapy-induced amenorrhea among breast cancer patients could affect almost half of the patients that undergo such therapy. However, some agents or therapeutic methods can ameliorate these intoxicating effects. Chemotherapy plus gonadotropin-releasing hormone agonist, in breast cancer patients, can not only improve overall survival but also reduce ovarian toxicity. Age plays an essential role in chemotherapy-induced amenorrhea. Chemotherapy at a younger age can reduce the risk of infertility. Gynecological cancers including uterine and ovarian cancer, which have high mortality rates, are the most related cancers to infertility. Surgery is the primary treatment of gynecological cancers. Studies demonstrated that fertility-sparing surgery is a better option than radical surgery. In addition, neoadjuvant chemotherapy is mostly a better option than primary cytoreductive surgery in terms of survival and fertility. Immune checkpoint inhibitors (ICIs) have recently played a major role in treating various cancer types. However, ICIs are associated with hypophysitis, which affects ovaries and can lead to infertility. There are some options for ovarian preservation such as embryo cryopreservation, oocyte cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and ovarian suppression by GnRH agonists. Anti-müllerian hormone level can be utilized to monitor the ovarian reserve. Moreover, to avoid fertility loss, approaches such as using transplantation of human placenta mesenchymal stem cells, administrating anti-inflammatory agents and hormone therapy are under investigation.

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin-microtubule System.

Modification of the tubulin-microtubule (Tub-Mts) system has generated effective strategies for developing different treatments for cancer. A huge amount of clinical data about inhibitors of the tubulin-microtubule system have supported and validated the studies on this pharmacological target. However, many tubulin-microtubule inhibitors have been developed from representative and common scaffolds that cover a small region of the chemical space with limited structural innovation. The main goal of this study is to develop the first consensus virtual screening protocol for natural products (ligand- and structure-based drug design methods) tuned for the identification of new potential inhibitors of the Tub-Mts system. A combined strategy that involves molecular similarity, molecular docking, pharmacophore modeling, and in silico ADMET prediction has been employed to prioritize the selections of potential inhibitors of the Tub-Mts system. Five compounds were selected and further studied using molecular dynamics and binding energy predictions to characterize their possible binding mechanisms. Their structures correspond to 5-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2,3-dimethoxyphenol (1), 9,10-dihydro-3,4-dimethoxy-2,7-phenanthrenediol (2), 2-(3,4-dimethoxyphenyl)-5,7-dihydroxy-6-methoxy-4H-1-benzopyran-4-one (3), 13,14-epoxyparvifoline-4',5',6'-trimethoxybenzoate (4), and phenylmethyl 6-hydroxy-2,3-dimethoxybenzoate (5). Compounds 1-3 have been associated with literature reports that confirm their activity against several cancer cell lines, thus supporting the utility of this protocol.

Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation: A Systematic Review.

Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO).

Explaining the interaction of mangiferin with MMP-9 and NF-ƙß: a computational study.

Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κß are characterized by using computational chemistry methods. The results show MMP-9 inhibition by mangiferina is characterized for the interact with the catalytic Zn atom through a penta-coordinate structure. It is also demonstrated through a strong charge transfer established between mangiferin and Zn in the QM/MM study. Concerning the mangiferin/NF-κß system, the 92.3% of interactions between p50 sub-unity and DNA are maintained with a binding energy of - 8.04 kcal/mol. These findings indicate that mangiferin blocks the p50-p65/DNA interaction resulting in the loss of the functions of this hetero-dimeric member and suggesting inhibition of the cancer progression. Experimental results concerning the anti-cancer properties of mangiferin show that this natural compound can inhibit selectively MMP-9 and NF-ƙß. Although the anti-tumor properties of mangiferin are well defined, its molecular mechanisms of actions are not described. In this work, a computational study is carried out to characterize the interactions of mangiferin with these molecular targets. The results obtained corroborate the anti-proliferative and anti-apoptotic activity of mangiferin and provide a depiction of its mechanisms of action.

Health from Brazilian Amazon food wastes: Bioactive compounds, antioxidants, antimicrobials, and potentials against cancer and oral diseases.

Brazilian Amazon contains over 30,000 plant species and foods rich in bioactive compounds such as terpenes, phenolic acids, alkaloids, and flavonoids, of potential health benefits (antioxidant, antimicrobial, antiparasitic, anticancer, gastroprotection, prebiotic effects, among others). The existence of residues from non-edible parts of plants (leaves, roots, stems, branches, barks) or fruit wastes (peel, bagasse, seeds) in the agri-food industry and its supply chain is an important challenge in food loss and waste management. In this critical review several Amazon species, focusing on extracts/essential oils from nonedible parts or wastes, were analyzed in terms of phytochemicals, biological activity, and underlying mechanisms. We hope this review emphasizes the importance of Amazon's sustainability initiatives on population health due to the potential shown against cancer, infectious diseases, and prevention of oral diseases. It is urgent to think about the conversion of amazon food wastes and co-products into high-added-value raw materials to develop novel drugs, food packaging systems, or nutraceutical foods.

A novel second-generation platinum derivative and evaluation of its anti-cancer potential

Abstract Cisplatin is the primary anti-cancer agent for the treatment of most solid tumors. However, platinum-based anti-cancer chemotherapy produces severe side effects due to its poor specificity. There are a broad interest and literature base for a novel mechanism of action on platinum derivatives. Additionally, combining cisplatin with histone deacetylase inhibitors (HDACi) such as 4-hydroxybenzoic acid derivatives showed promising results in treating solid tumors. Here we aimed to conjugate 4-hydroxybenzoic acid with platinum to obtain a novel platinum derivative that can overcome cisplatin resistance. Cis-4-hydroxyphenylplatinum(II)diamine compound was synthesized under mild conditions and characterized. Cytotoxicity assay was performed on SKOV3-Luc and A549-Luc cells. Hemocompatibility and serum protein binding analysis were performed. Treatment potential was evaluated in xenograft tumor models. Biodistribution was tested on tumor-bearing mice via Pt analysis in organs with ICP-MS, ex vivo. In this study, cis-4-hydroxyphenylplatinum (II) diamine was synthesized with a yield of 62%. The MTT assay on A549-Luc and SKOV3-Luc cell lines resulted in IC50 values of 17.82 and 7.81 µM, respectively. While tumor growth was continued in the control group, the tumor volume decreased in the treatment group. All results point to the conclusion that the new compound has the potential to treat solid tumors