antimitotic activity
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Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7139
Author(s):  
Pedro Novais ◽  
Patrícia M. A. Silva ◽  
Joana Moreira ◽  
Andreia Palmeira ◽  
Isabel Amorim ◽  
...  

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.


2021 ◽  
Vol 02 ◽  
Author(s):  
Sharon Riaz ◽  
Khalid Mohammed Khan ◽  
Ghayoor Abbas Chotana ◽  
Amir Faisal ◽  
Rahman Shah Zaib Saleem

: The substantial antimitotic potential of podophyllotoxin and its derivatives has attracted both synthetic and medicinal chemists to expand the chemical space for the subsequent biological evaluation of these compounds. The interest ranges from total synthesis, hemi-synthesis, one-pot synthetic approaches and structure-activity relationship studies. In the first segment of the review, we present recent development in the synthesis of podophyllotoxin and also describe its mode of action. The second section covers the synthesis and the structure-activity relationships of podophyllotoxin derivatives, along with the discussion of important structural features required by the molecule for displaying antimitotic activity. The last part describes the synthesis and biological evaluation of potent 4-aza podophyllotoxin derivatives. This review is of interest to chemists who study natural and synthetic compounds for drug discovery.


2021 ◽  
Vol 14 (11) ◽  
pp. 1119
Author(s):  
Azizah M. Malebari ◽  
Shu Wang ◽  
Thomas F. Greene ◽  
Niamh M. O’Boyle ◽  
Darren Fayne ◽  
...  

Antimitotic drugs that target tubulin are among the most widely used chemotherapeutic agents; however, the development of multidrug resistance has limited their clinical activity. We report the synthesis and biological properties of a series of novel 3-chloro-β-lactams and 3,3-dichloro-β-lactams (2-azetidinones) that are structurally related to the tubulin polymerisation inhibitor and vascular targeting agent, Combretastatin A-4. These compounds were evaluated as potential tubulin polymerisation inhibitors and for their antiproliferative effects in breast cancer cells. A number of the compounds showed potent activity in MCF-7 breast cancer cells, e.g., compound 10n (3-chloro-4-(3-hydroxy-4-methoxy-phenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one) and compound 11n (3,3-dichloro-4-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-azetidin-2-one), with IC50 values of 17 and 31 nM, respectively, and displayed comparable cellular effects to those of Combretastatin A-4. Compound 10n demonstrated minimal cytotoxicity against non-tumorigenic HEK-293T cells and inhibited the in vitro polymerisation of tubulin with significant G2/M phase cell cycle arrest. Immunofluorescence staining of MCF-7 cells confirmed that β-lactam 10n caused a mitotic catastrophe by targeting tubulin. In addition, compound 10n promoted apoptosis by regulating the expression of pro-apoptotic protein BAX and anti-apoptotic proteins Bcl-2 and Mcl-1. Molecular docking was used to explore the potential molecular interactions between novel 3-chloro-β-lactams and the amino acid residues of the colchicine binding active site cavity of β-tubulin. Collectively, these results suggest that 3-chloro-2-azetidinones, such as compound 10n, could be promising lead compounds for further clinical anti-cancer drug development.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zarrin Banikazemi ◽  
Seyed Mohammad Mirazimi ◽  
Fatemeh Dashti ◽  
Mohammad Reza Mazandaranian ◽  
Maryam Akbari ◽  
...  

Cancers of the gastrointestinal (GI) tract are often life-threatening malignancies, which can be a severe burden to the health care system. Globally, the mortality rate from gastrointestinal tumors has been increasing due to the lack of adequate diagnostic, prognostic, and therapeutic measures to combat these tumors. Coumarin is a natural product with remarkable antitumor activity, and it is widely found in various natural plant sources. Researchers have explored coumarin and its related derivatives to investigate their antitumor activity, and the potential molecular mechanisms involved. These mechanisms include hormone antagonists, alkylating agents, inhibitors of angiogenesis, inhibitors of topoisomerase, inducers of apoptosis, agents with antimitotic activity, telomerase inhibitors, inhibitors of human carbonic anhydrase, as well as other potential mechanisms. Consequently, drug design and discovery scientists and medicinal chemists have collaborated to identify new coumarin-related agents in order to produce more effective antitumor drugs against GI cancers. Herein, we summarize the therapeutic effects of coumarin and its derivatives against GI cancer.


Author(s):  
ANUSHA KOTHA ◽  
MUNI SIREESHA S. ◽  
ASHMA MD ◽  
JYOTHI VEMURI ◽  
SARITHA JYOSTNA T.

Objective: The present study was designed to study the anticancer activity of a series of novel analogs of phenothiazine with dithiocarbamate as a side chain. Methods: A novel series of derivatives containing dithiocarbamate as a side chain at the tenth position of phenothiazine nucleus were synthesized, characterized by spectral analysis, and evaluated for their antimitotic and antioxidant activity using germinated Bengal gram seeds and 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, respectively. A quantitative estimate of drug-likeness was also performed, which calculated the molecular properties and screened the molecules based on drug-likeness rules. Further, molecular docking study was performed for finding the binding affinity with tubulin protein to rationalize their anticancer activity. Results: The results revealed that the antioxidant activity of compounds 3e, 3g, 3i, 3j and standard Ascorbic acid were 10 mmol, 14 mmol, 16 mmol, 16 mmol and 35 mmol, respectively. Further compounds 3e, 3g, 3h and 3i have shown promising antimitotic activity. Compound 3i (-9 K. Cal/mol) showed the highest binding energies towards tubulin protein when compared to standard drug colchicine (-8.6 K. Cal/mol). Among all, compound 3i showed promising antimitotic and antioxidant activity, which correlated with insilico docking studies. Conclusion: Dithiocarbamate substituted phenothiazine derivatives proved to be encouraging leads as tubulin inhibitors.


Author(s):  
Nadar Sowmya ◽  
Chouhan Raghavendra Singh ◽  
Kosha Patel ◽  
Harshil Patel ◽  
Tanvi Dodiya ◽  
...  

According to the literature survey most of the studies done on Adarak (Zingiber officinale rhizome) were performed on alcoholic extracts or isolated entities of ginger but no profound work has been done on the traditionally prepared or commonly consumed way of ginger. So, in this current study, fresh ginger rhizomes were traditionally pounded to make Adarak juice. The different concentration (0.05%, 0.5%, 1%, 2.5%, 5%, 10%) were taken as sample to perform onion root tip inhibition assay and brine shrimp lethality bioassay. It showed antimitotic inhibition in the range of 0.05-10% concentration with an IC50 value of 0.37 % on number of rootlets was 0.08 % on length of rootlets. The traditionally prepared Adarak juice showed cytotoxicity in the range of 0.05-2.5% concentration with LC50 value of 1.59%. The traditionally prepared Adarak juice possesses cytotoxic and antimitotic activity.


Author(s):  
Nishita Gogia ◽  
Anandhi D ◽  
Kanaga G ◽  
Revathi K

The scope of the present study was to evaluate the In-vitro biological potential of Green synthesized silver nanoparticles from Chromolaena odorata, Caesalpinia coriaria (Bark) and Caesalpinia coriaria (Leaf). We investigated the effect of green synthesized silver nanoparticles from Chromolaena odorata, Caesalpinia coriaria (Bark) and Caesalpinia coriaria (Leaf) by studying anti-mitotic activity An attempt has been made to evaluate the anti-mitotic activity of silver nanoparticles using Allium cepa roots. The mitotic index of the root tips meristem was calculated and compared with the standard methotrexate. Antimitotic activity results shows the mitotic index was ranged from 30-40%. Green synthesized silver nanoparticles from Chromolaena odorato, Caesalpinia coriaria (Bark) and Caesalpinia coriaria (Leaf) possess significant anti-mitotic activity.


Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3057
Author(s):  
Kamila Buzun ◽  
Anna Kryshchyshyn-Dylevych ◽  
Julia Senkiv ◽  
Olexandra Roman ◽  
Andrzej Gzella ◽  
...  

A series of novel 5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-thiazolidinones (Ciminalum–thiazolidinone hybrid molecules) have been synthesized. Anticancer activity screening toward the NCI60 cell lines panel, gastric cancer (AGS), human colon cancer (DLD-1), and breast cancer (MCF-7 and MDA-MB-231) cell lines allowed the identification of 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (2h) with the highest level of antimitotic activity with mean GI50/TGI values of 1.57/13.3 μM and a certain sensitivity profile against leukemia (MOLT-4, SR), colon cancer (SW-620), CNS cancer (SF-539), melanoma (SK-MEL-5), gastric cancer (AGS), human colon cancer (DLD-1), and breast cancers (MCF-7 and MDA-MB-231) cell lines. The hit compounds 2f, 2i, 2j, and 2h have been found to have low toxicity toward normal human blood lymphocytes and a fairly wide therapeutic range. The significant role of the 2-chloro-3-(4-nitrophenyl)prop-2-enylidene (Ciminalum) substituent in the 5 position and the substituent’s nature in the position 3 of core heterocycle in the anticancer cytotoxicity levels of 4-thiazolidinone derivatives have been established


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chieh-Ting Fang ◽  
Hsiao-Hui Kuo ◽  
Chia-Jung Yuan ◽  
Jhong-Syuan Yao ◽  
Ling-Huei Yih

AbstractTaxol is a first-line chemotherapeutic for numerous cancers, including the highly refractory triple-negative breast cancer (TNBC). However, it is often associated with toxic side effects and chemoresistance in breast cancer patients, which greatly limits the clinical utility of the drug. Hence, compounds that act in concert with taxol to promote cytotoxicity may be useful to improve the efficacy of taxol-based chemotherapy. In this study, we demonstrated that mdivi-1, a putative inhibitor of mitochondrial fission protein Drp1, enhances the anticancer effects of taxol and overcomes taxol resistance in a TNBC cell line (MDA-MB-231). Not only did mdivi-1 induce mitotic spindle abnormalities and mitotic arrest when used alone, but it also enhanced taxol-induced antimitotic effects when applied in combination. In addition, mdivi-1 induced pronounced spindle abnormalities and cytotoxicity in a taxol-resistant cell line, indicating that it can overcome taxol resistance. Notably, the antimitotic effects of mdivi-1 were not accompanied by prominent morphological or functional alterations in mitochondria and were Drp1-independent. Instead, mdivi-1 exhibited affinity to tubulin at μM level, inhibited tubulin polymerization, and immediately disrupted spindle assembly when cells entered mitosis. Together, our results show that mdivi-1 associates with tubulin and impedes tubulin polymerization, actions which may underlie its antimitotic activity and its ability to enhance taxol cytotoxicity and overcome taxol resistance in MDA-MB-231 cells. Furthermore, our data imply a possibility that mdivi-1 could be useful to improve the therapeutic efficacy of taxol in breast cancer.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 622
Author(s):  
Maphuti T. Lebelo ◽  
Anna M. Joubert ◽  
Michelle H. Visagie

Recent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was assessed in the activity exerted by ESE-one on cell cycle progression, mitochondrial membrane potential and cell death induction in breast tumorigenic cells. The influence of ESE-one was also investigated on superoxide dismutase and catalase activity. ESE-one induced a time-dependent accumulation of cells in the G1 phase and G2/M phase that is partially impaired by tiron and trolox and N,N′-dimethylthiourea suggesting that superoxide anion, hydrogen peroxide and peroxyl radical are required for these effects exerted by ESE-one. Flow cytometry data in MCF-7 cells demonstrated that tiron decreased depolarization of the membrane potential in ESE-one exposed cells, indicating that superoxide anion plays a role in the depolarization effects induced by ESE-one. Spectrophotometry data showed that ESE-one decreased catalase activity in both cell lines. This study contributes towards pertinent information regarding the effects of an in silico-designed sulfamoylated compound on antioxidant enzymes leading to aberrant quantities of specific reactive oxygen species resulting in antimitotic activity culminating in the induction of cell death in breast cancer cell lines.


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