Novel Aspects of Natural and Modified Vinca Alkaloids

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

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Tubulin Proteins in Cancer Resistance: A Review

Current Drug Metabolism ◽

10.2174/1389200221666200226123638 ◽

2020 ◽

Vol 21 (3) ◽

pp. 178-185 ◽

Cited By ~ 1

Author(s):

Mohammad Amjad Kamal ◽

Maryam Hassan Al-Zahrani ◽

Salman Hasan Khan ◽

Mateen Hasan Khan ◽

Hani Awad Al-Subhi ◽

...

Keyword(s):

Cell Cycle ◽

Cancer Cells ◽

High Rate ◽

Vinca Alkaloids ◽

Cancer Resistance ◽

New Approach ◽

Natural Sources ◽

Cell Cycle Genes ◽

Cancerous Cells ◽

Β Tubulin

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

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Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms22041980 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1980

Author(s):

Mariarita Laforgia ◽

Carmelo Laface ◽

Concetta Calabrò ◽

Simona Ferraiuolo ◽

Valentina Ungaro ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Health Professionals ◽

Life Experience ◽

The Other ◽

Vinca Alkaloids ◽

Neurologic Complications ◽

Typically Develop ◽

Hospital Pharmacists ◽

Single Mechanism

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients’ quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effect, but the genesis of chemotherapy-induced peripheral neuropathy is not linked to a single mechanism. This paper aims from one side at summarizing and explaining all the scattering mechanisms of chemotherapy-induced peripheral neuropathy through a detailed literature revision, on the other side at finding new approaches to possible treatments, in order to facilitate the collaboration between oncologists, hematologists and hospital pharmacists.

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ChemInform Abstract: Synthesis of Vinca Alkaloids and Related Compounds. Part 65. Preparation of 7-Methoxytryptamine.

ChemInform ◽

10.1002/chin.199405266 ◽

2010 ◽

Vol 25 (5) ◽

pp. no-no

Author(s):

F. SOTI ◽

M. INCZE ◽

Z. KARDOS-BALOGH ◽

M. KAJTAR-PEREDY ◽

C. SZANTAY

Keyword(s):

Vinca Alkaloids ◽

Related Compounds

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Preclinical and Clinical Pharmacology of Vinca Alkaloids

Drugs ◽

10.2165/00003495-199200444-00002 ◽

1992 ◽

Vol 44 (Supplement 4) ◽

pp. 1-16 ◽

Cited By ~ 92

Author(s):

Xiao-Jian Zhou ◽

Roger Rahmani

Keyword(s):

Clinical Pharmacology ◽

Vinca Alkaloids

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The Stability of Antineoplastic Vinca Alkaloids in Plasma and Urine

Bioanalysis of Drugs and Metabolites, Especially Anti-Inflammatory and Cardiovascular ◽

10.1007/978-1-4757-9424-3_40 ◽

1988 ◽

pp. 283-288

Author(s):

D. E. M. M. Vendrig ◽

A. Mekking ◽

J. Teeuwsen ◽

J. J. M. Holthuis

Keyword(s):

Vinca Alkaloids ◽

The Stability

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Fighting tubulin-targeting anticancer drug toxicity and resistance

Endocrine Related Cancer ◽

10.1530/erc-17-0120 ◽

2017 ◽

Vol 24 (9) ◽

pp. T107-T117 ◽

Cited By ~ 17

Author(s):

Roberta Visconti ◽

Domenico Grieco

Keyword(s):

Drug Toxicity ◽

Kinase Activity ◽

Triple Negative ◽

Molecular Targets ◽

Vinca Alkaloids ◽

Drug Resistant ◽

Castration Resistant Prostate Cancer ◽

Mitotic Progression ◽

Castration Resistant

Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle. Other possible treatments that improve outcomes in the clinic for these two drug-resistant cancers, including new formulations of the AMCDs and pursuing different molecular targets, will be discussed.

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