Synthesis and Investigation of Conformationally Restricted Analogues of Lavendustin A as Cytotoxic Inhibitors of Tubulin Polymerization

2002 ◽  
Vol 45 (21) ◽  
pp. 4774-4785 ◽  
Author(s):  
Fanrong Mu ◽  
Debbie J. Lee ◽  
Donald E. Pryor ◽  
Ernest Hamel ◽  
Mark Cushman
Keyword(s):  
Tubulin Polymerization ◽  
Conformationally Restricted

Synthesis, Anticancer Activity, and Inhibition of Tubulin Polymerization by Conformationally Restricted Analogues of Lavendustin A

2003 ◽  
Vol 46 (9) ◽  
pp. 1670-1682 ◽  
Author(s):  
Fanrong Mu ◽  
Ernest Hamel ◽  
Debbie J. Lee ◽  
Donald E. Pryor ◽  
Mark Cushman
Keyword(s):  
Anticancer Activity ◽  
Tubulin Polymerization ◽  
Conformationally Restricted

Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

1977 ◽  
Vol 35 ◽  
pp. 460-461
Author(s):  
Tai-Te Chao ◽  
John Sullivan ◽  
Awtar Krishan
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Transmission Electron Microscopy ◽  
Tubulin Polymerization ◽  
Vinca Alkaloids ◽  
Antimitotic Activity ◽  
Transmission Electron ◽  
Flow Microfluorometry ◽  
Brain Tubulin

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.

Synthesis and Biological Activity of Quaternary Quinolinium Salts: A Review

2020 ◽  
Vol 23 (21) ◽  
pp. 2271-2294 ◽  
Author(s):  
Divya Utreja ◽  
Shivali Sharma ◽  
Akhil Goyal ◽  
Komalpreet Kaur ◽  
Sonia Kaushal
Keyword(s):  
Tyrosine Kinases ◽  
Biological Activities ◽  
Polymeric Materials ◽  
Tubulin Polymerization ◽  
Quinoline Derivatives ◽  
Heterocyclic Chemistry ◽  
Biological Profile ◽  
Drug Candidates ◽  
Anti Hiv ◽  
Quinolinium Salts

Heterocyclic chemistry is the only branch of chemistry that has applications in varied areas such as dyes, photosensitizers, coordination compounds, polymeric materials, biological, and many other fields. Quinoline and its derivatives have always engrossed both synthetic chemists and biologists because of their diverse chemical and pharmacological properties as these ring systems can be easily found in various natural products, especially in alkaloids. Among alkaloids, quinoline derivatives i.e. quinolinium salts have attracted much attention nowadays owing to their diverse biological profile such as antimicrobial, antitumor, antifungal, hypotensive, anti-HIV, analgesics and anti-inflammatory, etc. Quinoline and its analogs have recently been examined for their modes of function in the inhibition of tyrosine kinases, proteasome, tubulin polymerization, topoisomerase, and DNA repair. These observations have been guiding scientists for the expansion of new quinoline derivatives with improved and varied biological activities. Quinolinium salts have immense possibilities and scope to investigate these compounds as potential drug candidates. Therefore, we shall present a concise compilation of this work to aid in present knowledge and to help researchers explore an interesting quinoline class having medicinal potential.

Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Tubulin Polymerization ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Colchicine Binding Site ◽  
Anti Cancer

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking

2019 ◽  
Vol 19 (4) ◽  
pp. 439-452 ◽  
Author(s):  
Mohamed R. Selim ◽  
Medhat A. Zahran ◽  
Amany Belal ◽  
Moustafa S. Abusaif ◽  
Said A. Shedid ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Caspase 3 ◽  
Biological Evaluation ◽  
Tubulin Polymerization ◽  
Design Synthesis ◽  
Chemical Structures ◽  
M Phase ◽  
Induced Apoptosis ◽  
Derivatives Of

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

Synthesis and tubulin interaction of thiocolchicines containing an isothiocyanato group. Synthesis of C(2)-deuterated and C(2)-14C-labeled 7-isothiocyanatodeacetamidothiocolchicine

1991 ◽  
Vol 56 (11) ◽  
pp. 2306-2312 ◽  
Author(s):  
Anjum Muzaffar ◽  
Ernest Hamel ◽  
Rouli Bai ◽  
Arnold Brossi
Keyword(s):  
Binding Site ◽  
Covalent Bond ◽  
Tubulin Polymerization ◽  
Low Concentration ◽  
Covalent Interaction ◽  
Isotope Label ◽  
Colchicine Binding Site

Synthesis of isothiocyanato substituted thiocolchicines XI - XIV is described. Introduction of an isotope label is demonstrated with the deuterated isothiocyanate XII and the 14C-labeled analog XIII. These isothiocyanates inhibit tubulin polymerization at low concentration. In addition, the 14C-labeled XIII forms covalent bond(s) with tubulin. Unfortunately, the covalent reaction while rapid, is not inhibited by preincubation of tubulin with colchicine. The covalent interaction of XIII with tubulin thus appears to be nonspecific, limiting its use as a marker of the colchicine binding site on tubulin.

scholarly journals Simple Thalidomide Analogs in Melanoma: Synthesis and Biological Activity

2021 ◽  
Vol 11 (13) ◽  
pp. 5823
Author(s):  
Alexia Barbarossa ◽  
Alessia Catalano ◽  
Jessica Ceramella ◽  
Alessia Carocci ◽  
Domenico Iacopetta ◽  
...  
Keyword(s):  
Anticancer Agent ◽  
Ring System ◽  
In Vitro Assays ◽  
Tubulin Polymerization ◽  
Cytotoxic Effects ◽  
Ongoing Research ◽  
Drug Candidates ◽  
Small Series ◽  
Clinical Interest

Thalidomide is an old well-known drug that is still of clinical interest, despite its teratogenic activities, due to its antiangiogenic and immunomodulatory properties. Therefore, efforts to design safer and effective thalidomide analogs are continually ongoing. Research studies on thalidomide analogs have revealed that the phthalimide ring system is an essential pharmacophoric fragment; thus, many phthalimidic compounds have been synthesized and evaluated as anticancer drug candidates. In this study, a panel of selected in vitro assays, performed on a small series of phthalimide derivatives, allowed us to characterize compound 2k as a good anticancer agent, acting on A2058 melanoma cell line, which causes cell death by apoptosis due to its capability to inhibit tubulin polymerization. The obtained data were confirmed by in silico assays. No cytotoxic effects on normal cells have been detected for this compound that proves to be a valid candidate for further investigations to achieve new insights on possible mechanism of action of this class of compounds as anticancer drugs.

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