scholarly journals Total syntheses of the archazolids: an emerging class of novel anticancer drugs

2017 ◽  
Vol 13 ◽  
pp. 1085-1098 ◽  
Author(s):  
Stephan Scheeff ◽  
Dirk Menche
Keyword(s):  
Total Synthesis ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Preclinical Development ◽  
Total Syntheses ◽  
Atpase Inhibitors ◽  
Anticancer Target

V-ATPase has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with the archazolids, complex polyketide macrolides which present the most potent V-ATPase inhibitors known to date, rendering these macrolides important lead structures for the development of novel anticancer agents. The limited natural supply of these metabolites from their myxobacterial source renders total synthesis of vital importance for the further preclinical development. This review describes in detail the various tactics and strategies employed so far in archazolid syntheses that culminated in three total syntheses and discusses the future synthetic challenges that have to be addressed.

scholarly journals Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1412
Author(s):  
Maria Grazia Ferraro ◽  
Marialuisa Piccolo ◽  
Gabriella Misso ◽  
Francesco Maione ◽  
Daniela Montesarchio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Drugs ◽  
Anticancer Agents ◽  
Preclinical Development ◽  
Cell Death Pathways ◽  
Complex Information ◽  
Ru Complexes ◽  
Therapeutic Alternatives

In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium-based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple-negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced next-generation metallotherapeutics, with NAMI-A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well-known NAMI-A complex, information on non-nanostructured Ru-based anticancer agents have been included in a precise manner.

scholarly journals In Vitro and In Vivo Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Mamoudou Maiga ◽  
Seong Won Choi ◽  
Viorel Atudorei ◽  
Mariama C. Maiga ◽  
Zachary D. Sharp ◽  
...  
Keyword(s):  
Breath Test ◽  
Point Of Care ◽  
In Vivo Studies ◽  
Co Dehydrogenase ◽  
Preclinical Development ◽  
Breath Tests ◽  
Monitoring Therapy ◽  
Effective Diagnosis

ABSTRACTOne of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism’s CO dehydrogenase activity. After development of the testin vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host.IMPORTANCETuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2.

scholarly journals ANTICANCER ACTIVITY OF UPAVISHA ARKA: AN OVERVIEW

2020 ◽  
Vol 9 (6) ◽  
pp. 175-181
Author(s):  
Chandekar Deepali Boudhadas ◽  
Pawade Uday Venkatrao ◽  
Nikam Ashwin Vithalrao ◽  
Anjankar Meghsham Pramodrao
Keyword(s):  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Cost Effective ◽  
In Vivo Studies ◽  
Calotropis Procera ◽  
Calotropis Gigantea ◽  
Natural Derivative

Cancer is one amongst the dreadful diseases of present century. The incidence of cancer is increasing worldwide. Every year about 8,00,000 new cancer patients get registered with the national cancer registry program in India. Ayurveda an ancient Indian medicine science describes many useful herbal drugs for such types of advanced diseases. Upavisha the plant poisons of low potency are mentioned in Agadtantra. Arka (Calotropis procera/ Calotropis gigantea) is one among these Upavisha is emerging as an effective anticancer drug. It shows various pharmacological activities such as Anticancer, Antimicrobial, Antiimplantation etc. Different parts of Arka are used to treat cancer. In current scenario number of synthetic anticancer drugs are used to treat cancer. These synthetic anticancer drugs are expensive and shows harmful adverse effects. Upavisha like Arka which is natural derivative may be cost effective & less harmful as Anticancer drug. Anticancer activity of Calotropis procera/Calotropis gigantea is reported in scientific journals. This review summarizes various In Vitro and In Vivo studies of anticancer activity of Upavisha Arka.

Gold Nanoparticles as Targeted Delivery Systems and Theranostic Agents in Cancer Therapy

2019 ◽  
Vol 26 (35) ◽  
pp. 6493-6513 ◽  
Author(s):  
Alexandra Mioc ◽  
Marius Mioc ◽  
Roxana Ghiulai ◽  
Mirela Voicu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Theranostic Agents ◽  
Targeted Delivery Systems

Cancer is still a leading cause of death worldwide, while most chemotherapies induce nonselective toxicity and severe systemic side effects. To address these problems, targeted nanoscience is an emerging field that promises to benefit cancer patients. Gold nanoparticles are nowadays in the spotlight due to their many well-established advantages. Gold nanoparticles are easily synthesizable in various shapes and sizes by a continuously developing set of means, including chemical, physical or eco-friendly biological methods. This review presents gold nanoparticles as versatile therapeutic agents playing many roles, such as targeted delivery systems (anticancer agents, nucleic acids, biological proteins, vaccines), theranostics and agents in photothermal therapy. They have also been outlined to bring great contributions in the bioimaging field such as radiotherapy, magnetic resonance angiography and photoacoustic imaging. Nevertheless, gold nanoparticles are therapeutic agents demonstrating its in vitro anti-angiogenic, anti-proliferative and pro-apoptotic effects on various cell lines, such as human cervix, human breast, human lung, human prostate and murine melanoma cancer cells. In vivo studies have pointed out data regarding the bioaccumulation and cytotoxicity of gold nanoparticles, but it has been emphasized that size, dose, surface charge, sex and especially administration routes are very important variables.

Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract

2018 ◽  
Vol 16 (1) ◽  
pp. 78-91 ◽  
Author(s):  
Mateusz Pięt ◽  
Roman Paduch
Keyword(s):  
Gastrointestinal Tract ◽  
Side Effects ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Pentacyclic Triterpenoids ◽  
Liver Cancers ◽  
Anti Cancer ◽  
Tumorigenic Activity

Background:Cancer is one of the main causes of death worldwide. Contemporary therapies, including chemo- and radiotherapy, are burdened with severe side effects. Thus, there exists an urgent need to develop therapies that would be less devastating to the patient’s body. Such novel approaches can be based on the anti-tumorigenic activity of particular compounds or may involve sensitizing cells to chemotherapy and radiotherapy or reducing the side-effects of regular treatment.Objective:Natural-derived compounds are becoming more and more popular in cancer research. Examples of such substances are Ursolic Acid (UA) and Oleanolic Acid (OA), plant-derived pentacyclic triterpenoids which possess numerous beneficial properties, including anti-tumorigenic activity.Results:In recent years, ursolic and oleanolic acids have been demonstrated to exert a range of anticancer effects on various types of tumors. These compounds inhibit the viability and proliferation of cancer cells, prevent their migration and metastasis and induce their apoptosis. Both in vitro and in vivo studies indicate that UA and OA are promising anti-cancer agents that can prevent carcinogenesis at each step. Furthermore, cancers at all stages are susceptible to the activity of these compounds. </P><P> Neoplasms that are formed in the gastrointestinal tract, i.e. gastric, colorectal, pancreatic, and liver cancers, are among the most common and most lethal malignancies. Their localization in the digestive system, however, facilitates the action of orally-administered (potential) anti-cancer agents, making chemopreventive drugs more accessible.In this paper, the anti-tumorigenic effect of ursolic and oleanolic acids on gastric, colon, pancreatic, and liver cancers, as well as the mechanisms underlying this process, are presented.

Liposomes Co- encapsulating Anticancer Drugs in Synergistic Ratios as an Approach to Promote Increased Efficacy and Greater Safety

2019 ◽  
Vol 19 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Marina S. Franco ◽  
Mônica C. Oliveira
Keyword(s):  
Anticancer Agents ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
In Vivo Studies ◽  
Fixed Drug ◽  
The 1960S ◽  
The Individual ◽  
Tumor Eradication

The era of chemotherapy began in the 1940s, but it was in the 1960s that it was seen as really promising when the first patients with childhood acute lymphoblastic leukemia were cured with combination chemotherapy. Today, it is known that due to resistance to single agents, combination therapy is essential for tumor eradication and cure. In the last decade, studies have shown that anticancer drug combinations can act synergistically or antagonistically against tumor cells in vitro, depending on the ratios of the individual drugs forming the combination. From this observation and facing the possibility of maintaining the in vivo synergistic ratio of combinations came the idea of co-encapsulating anticancer agents in nanosystems. In vivo studies validated this idea by showing that the co-encapsulation of anticancer agents in liposomes allows the maintenance of drug ratios in the plasma and the delivery of fixed drug ratios directly to tumor tissue, leading to a better efficacy compared to the administration of the free drugs combination. Liposomes co-encapsulating irinotecan/floxuridine are now in Phase II trial, and liposomes co-encapsulating cytarabine/daunorubicin were recently approved by the FDA for treatment of patients with acute myeloid leukemia.

Generation of a Conditionally Transformed Murine Embryonic Fibroblast Cell Line Using Doxycycline-Dependent IGF-1R Overexpression

2011 ◽  
Vol 17 (3) ◽  
pp. 339-349
Author(s):  
Ralph Graeser ◽  
Patricia Vrignaud ◽  
Norbert Esser ◽  
Sarah Umber ◽  
Ute Zirrgiebel ◽  
...  
Keyword(s):  
Cell Line ◽  
Expression System ◽  
Tumor Therapy ◽  
In Vivo Studies ◽  
Inhibitory Antibody ◽  
Preclinical Development ◽  
Murine Embryonic Fibroblast ◽  
Cellular Models

The insulin-like growth factor I receptor (IGF1-R) system has long been implicated in cancer and is a promising target for tumor therapy. Besides in vitro screening assays, the discovery of specific inhibitors against IGF-1R requires relevant cellular models, ideally applicable to both in vitro and in vivo studies. With this aim in mind, the authors generated an inducible cell line using the tetracycline-responsive gene expression system to mimic the effects of therapeutic inhibition of the IGF-1R both in vitro and on established tumors in vivo. Inducible overexpression of IGF-1R in murine embryonic fibroblasts was achieved and resulted in the transformation of the cells as verified by their ability to grow in soft agar and in nude mice. Continuous repression of exogenous IGF-1R expression completely prevented outgrowth of the tumors. Furthermore, induced repression of IGF-1R expression in established tumors resulted in regression of the tumors. Interestingly, however, IGF-1R–independent relapse of tumor growth was observed upon prolonged IGF-1R repression. The IGF-1R cell line generated using this approach was successfully employed to test reference small-molecule inhibitors in vitro and an IGF-1R–specific inhibitory antibody, EM164, in vivo. Besides efficacy as a read-out, phospho-AKT could be identified as a pharmacodynamic biomarker, establishing this cell line as a valuable tool for the preclinical development of IGF-1R inhibitors.

scholarly journals In vitro and in vivo studies on potentiation of cytotoxic effects of anticancer drugs or cobalt 60 gamma ray by interferon on human neoplastic cells

Cancer ◽  
1984 ◽  
Vol 54 (10) ◽  
pp. 2262-2267 ◽  
Author(s):  
Masayoshi Namba ◽  
Shoichi Yamamoto ◽  
Hiroyoshi Tanaka ◽  
Toshinori Kanamori ◽  
Masahiro Nobuhara ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Gamma Ray ◽  
In Vivo Studies ◽  
Neoplastic Cells ◽  
Cytotoxic Effects
Sign in / Sign up

Export Citation Format

Share Document