Natural products and synthetic analogs as a source of antitumor drugs

Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs.This work was supported by CONICYT PIA/APOYO CCTE AFB170007

Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence

Chalcones are among the leading bioactive flavonoids with a therapeutic potential implicated to an array of bioactivities investigated by a series of preclinical and clinical studies. In this article, different scientific databases were searched to retrieve studies depicting the biological activities of chalcones and their derivatives. This review comprehensively describes preclinical studies on chalcones and their derivatives describing their immense significance as antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Besides, clinical trials revealed their use in the treatment of chronic venous insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and derivatives indicate possible hindrance and improvement in relation to its nutraceutical and pharmaceutical applications. Multifaceted and complex underlying mechanisms of chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to inhibit a number of pathological microorganisms and parasites, and to control a number of signaling molecules and cascades related to disease modification. Clinical studies on chalcones revealed general absence of adverse effects besides reducing the clinical signs and symptoms with decent bioavailability. Further studies are needed to elucidate their structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs

Review of the Urinary Schistosomiasis Control in Morocco (1960–2018)

The purpose of this study is to describe the epidemiological profile and evolution of urinary schistosomiasis in Morocco, from the first confirmed case in 1960 until disease elimination, and control snails. During this period, 129,526 cases were recorded in Morocco. A majority of cases were reported in Agadir province (25%), Errachidia (18%), and Beni Mellal (13%). Other cases have been reported in the other provinces. Activities within the National Schistosomiasis Control Programme for more than three decades were focused in priori on screening in schools located in high-risk communities, treatment program, surveillance of snails in water bodies, and mollusciciding. Then, the goal of eliminating the transmission of schistosomiasis has been reached in 2004. Sixteen years later, no indigenous cases were detected in Morocco, and only 25 residual cases (resulting from bilharziasis previously treated) are detected, such as in Tata ( 40%), Errachidia (16%), and (12%) in Marrackesh. Similarly, recent national studies conducted on children and the snail reservoir hosts have indicated that no human and molluscs are currently infected with Schistosoma haematobium. Actually, timely investigation and management of imported cases has been implemented to prevent the reintroduction of the disease. The Ministry of Health is planning to implement final confirmatory surveys before requesting WHO to proceed with the formal verification process

Survey and Diagnostic Challenges after Transmission-Stop: Confirming Elimination of Schistosomiasis haematobium in Morocco

Clinical cases of Moroccan residents have been recorded since 2004, indicating successful interruption of transmission of S. haematobium infection at national level. The first national survey initiated in 2009 for Schistosomiasis haematobium among children born after 2004, applied diagnostic test was the HAMA-EITB, based on the Western blot technology, and molecular malacological diagnostic tools clearly confirm transmission stop. In 2015, a recent, small survey utilizing an HAI, ELISA tests and an ultrasensitive antigen test, FTCUP CAA, in a group of individual with a past history of infection. However, obviously follow-up surveys to prevent reemergency and for certification of the schistosomiasis elimination require vigilant diagnosis strategies. Here we discuss diagnosis story line in the national laboratory and challenges based on the available tools in relation to their clinical parameters (sensitivity/specificity; Sn/Sp), practicability and associated costs. When transmission stop has been achieved, survey cost and speed are likely to benefit from cost effective pooling strategies and ultrasensitive assays indicating active infection in all potential risk groups. Similarly molecular pooling strategies to monitor infections in the snail vectors

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers

Comprehensive Overview On Nutritional, Phytochemistry And Pharmacological Properties Of Tetraclinis Articulata Masters

Tetraclinis articulata is a medicinal plant distributed from northwestern Africa to southwestern Europe. This article reports previous investigations on T. articulata regarding its taxonomy, botanical description, geographical distribution, traditional use, phytochemistry, biological effects, toxicology, nutritional value, and economic interest. The search of data was based on several scientific databases such as Scopus, Wiley Online, Web of Science, Google Scholar, PubMed, ScienceDirect, SciFinder, and SpringerLink. Indeed, several biological activities were reported for T. articulata extracts and EOs, including antioxidant, antibacterial, antifungal, anticorrosion, cytotoxic, insecticidal, leishmanicidal, larvicidal, anti-inflammatory, antidiarrheal, vasorelaxant, and protective activities. Moreover, some toxicological reports indicated that T. articulata does not present any toxicity. However, other investigations regarding the toxicity, the pharmacokinetic and the pharmacodynamics of T. articulata and its major bioactive compounds are required to validate its pharmacological use. T. articulata also contains some nutritional elements such as mineral compounds, sugar and proteins which could indicate its potential use in the nutraceutical field. All these properties to T. articulata attributed a major economic interest which is used actually in the manufacture of luxury varnishes, pharmaceutical products and in other industrial uses, it is also used in powder form to prepare the surface of certain paper