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In this work, nine 6-fluoro-triazolo-benzothiazole derivatives were prepared and evaluated for in vitro antimitotic activity. In addition, in silico study was also done using tubulin protein (PDB: 6QQN) by molecular docking method. Results revealed that TZ2 and TZ9 were the most active compounds with antimitotic action opposing the standard drug, aspirin. Results of molecular docking exhibited the inhibitory potential of triazolo-benzothiazole against tubulin protein. The mitotic study indicates the efficacy of triazolo-benzothiazole analogues in inhibiting the proliferation of cancer cells either by promoting microtubule formation or affecting microtubules, thereby preventing microtubule breakdown. [ABSTRACT FROM AUTHOR]

Vateria indica is persistent tree used in Unani sources for the medication and classified as critically endangered. Thus, endophytes for alternative methods to explore these endangered Plants having rich source pharmaceuticals' active molecules for drug development and production. Endophytes comprises unexplored microbes as a potential source of rich pharmaceutically bioactive compounds attributable to their relationship with the host. In the current study, we have isolated endophyte fungi Cladosporium from the plant Vateria indica and performed phytochemical screening of its ethanolic extract to detect the phytochemicals using thin layer chromatography (TLC), gas chromatography–mass spectrometry (GC–MS), high-performance liquid chromatography (HPLC), UV–visible spectrophotometry (UV–VIS), and Fourier transform infrared spectroscopy (FTIR). GC–MS analysis revealed the presence of an anticancer compound hydroxymethyl colchicine, antioxidant compound benzoic acid, and antimicrobial 2-(4-chlorophenoxy)-5-nitro in endophyte fungal extract of plant Vateria indica. Moreover, in silico analysis of bioactive compounds identified by GC–MS analysis using the Autodock Vina and SwissADME confirmed excellent anticancer activity methanone, [4-amino-2-[(phenylmethyl) amino]-5-thiazolyl] (4-fluorophenyl)- and hydroxymethyl colchicine against 6VO4 (Bfl-1 protein) as per Lipinski rule. Furthermore, we also demonstrated the excellent antioxidant of endophytic extract compared to plant extract by DPPH and ABTS assay, as well as antimicrobial activity against both Gram (+ ve) and Gram (− ve) bacteria. Moreover, the endophytic extract also showed its antimitotic activity with a mitotic index of 65.32, greater than the plant extract of 32.56 at 10 mg/ml. Thus endophytic fungi Cladosporium species isolated from plant Vateria indica might be used as a potential source for phytochemical anticancer hydroxymethyl colchicine, an antioxidant benzoic acid, and antimicrobial 2-(4-chlorophenoxy)-5-nitro. [ABSTRACT FROM AUTHOR]

A series of colchicine and thiocolchicine derivatives bearing a Michael acceptor moiety in ring A were synthesized. Some of these compounds exhibit cytotoxic activity in the nanomolar range, efficiently disrupt the mitotic spindle, and cause the accumulation of G2/M-phase cells resulting in the development of apoptosis. These derivatives can be covalently bound to the cysteine residues at the colchicine-binding site of tubulin. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is the second leading disease responsible for causing death worldwide. Under normal circumstances, cells of living creatures undergo division. However, excessive cell division is one of hallmarks of cancer. Efforts are used to treat cancer with low side effects by using herbs which are potential to act as anti-mitotic substances, such as pigeon pea (Cajanus cajan) which contains flavonoids, tannins, alkaloids, saponins, cyanogenic glycosides, glycosides, and anthocyanins which have the anti-inflammatory, anti-cancer, immunomodulatory, and also antioxidants properties. The study aims to determine the anti-mitotic activity of the pigeon pea (Cajanus cajan) filtrates to sea urchin (Diadema antillarum) embryonic cells. Methods: This study was experimental research in laboratory. This study used 5 replications for each dose of filtrates (5%, 10%, 15%, 20% and 25%) and cell division processes was observed at following specific time: every 15 minutes until the first division stage (to produce 2 cells), every 1 hour for the second division stage (to produce 4, 8, 16, and 32 cells) and every 24 hours to microscopically observe the blastula, gastrula and plateus. The results were observed in 10 high-power fields. Data were then analyzed with an ANOVA test using IBM SPSS 25. Results: The result shows that on every treatment groups there was a decrease in the percentage of sea urchin embryonic cells which underwent division at each stage of cell division and was significantly different (P<0.05). Conclusion: Pigeon pea filtrates showed an antimitotic activity to sea urchin embryonic cells (P<0.05). [ABSTRACT FROM AUTHOR]

[Display omitted] Monomethoxy substituted o -diarylazoles with isoxazole, triazole, pyrazole, or pyrrole linkers were synthesized and evaluated for antimitotic antitubulin activity in a sea urchin embryo model. Structure–activity relationship study revealed that only isoxazole heterocycle together with the unsubstituted phenyl ring next to the heteroatom endowed the molecule with appropriate configuration to exhibit antiproliferative effect by microtubule destabilizing mode of action. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women worldwide. Estrogen receptor-positive (ER+) breast cancer represents approximately 75% of diagnosed cases, while 15–20% of them are triple-negative (TN). Although there have been improvements in the therapeutic approach, the mortality rate remains elevated. Thus, it is necessary to identify new chemotherapeutic agents. The present study aimed to evaluate the effects of calein C, a sesquiterpene lactone isolated from Calea pinnatifida, on breast cancer cell lines MCF-7 (ER+), Hs578T (TN) and MDA-MB-231 (TN). Calein C significantly reduced the viability of all cell lines; however, MCF-7 cells were more responsive than MDA-MB-231 or Hs578T cells. Thus, the MCF-7 cell line was selected for further investigation. We demonstrated that calein C inhibited cell cycle progression in MCF-7 cells at M-phase. Increased frequency of mitosis was observed in calein C-treated samples compared to the control group, especially of the cell population in initial stages of the mitosis. These events were associated with the ability of calein C to modulate expression levels of critical regulators of mitosis progression. We observed a significant reduction in the relative mRNA abundance of PLK1 and AURKB along with a concomitant increase in CDKN1A (p21) in treated samples. In addition, calein C induced apoptosis in MCF-7 cells due to, at least in part, its ability to reduce the BCL2/BAX ratio. Therefore, our data provide evidence that calein C is an important antimitotic agent and should be considered for further in vivo investigations.

Graphical abstract Highlights • Estradiol dimer inhibits tubulin assembly in vitro. • Estradiol dimer reversibly disrupts microtubule structures in U2OS cells. • Estradiol dimer inhibits microtubule dynamics in U2OS cells. • Estradiol dimer shows cytotoxic activities on cancer cell lines, arrests cells in the G2/M phase of the cell cycle and attenuates DNA/RNA synthesis. • Estradiol dimer has no effect on the transactivation by estrogen receptor α. Abstract Microtubule dynamics is one of the major targets for new chemotherapeutic agents. This communication presents the synthesis and biological profiling of steroidal dimers based on estradiol, testosterone and pregnenolone bridged by 2,6-bis(azidomethyl)pyridine between D rings. The biological profiling revealed unique properties of the estradiol dimer including cytotoxic activities on a panel of 11 human cell lines, ability to arrest in the G2/M phase of the cell cycle accompanied with the attenuation of DNA/RNA synthesis. Thorough investigation precluded a genomic mechanism of action and revealed that the estradiol dimer acts at the cytoskeletal level by inhibiting tubulin polymerization. Further studies showed that estradiol dimer, but none of the other structurally related dimeric steroids, inhibited assembly of purified tubulin (IC 50 , 3.6 μM). The estradiol dimer was more potent than 2-methoxyestradiol, an endogenous metabolite of 17β-estradiol and well-studied microtubule polymerization inhibitor with antitumor effects that was evaluated in clinical trials. Further, it was equipotent to nocodazole (IC 50 , 1.5 μM), an antimitotic small molecule of natural origin. Both estradiol dimer and nocodazole completely and reversibly depolymerized microtubules in interphase U2OS cells at 2.5 μM concentration. At lower concentrations (50 nM), estradiol dimer decreased the microtubule dynamics and growth life-time and produced comparable effect to nocodazole on the microtubule dynamicity. In silico modeling predicted that estradiol dimer binds to the colchicine-binding site in the tubulin dimer. Finally, dimerization of the steroids abolished their ability to induce transactivation by estrogen receptor α and androgen receptors. Although other steroids were reported to interact with microtubules, the estradiol dimer represents a new structural type of steroid inhibitor of tubulin polymerization and microtubule dynamics, bearing antimitotic and cytotoxic activity in cancer cell lines. [ABSTRACT FROM AUTHOR]

The Barton-Zard reaction of nitro substituted stilbenes and chalcones with ethyl isocyanoacetate afforded 3,4-diaryl- and 4-acyl-3-arylpyrroles, respectively. 3-Arylpyrrole-2,4- dicarboxylates and 4-arylisoxazoline N-oxides were side reaction products. Antimitotic activity of target 3,4-disubstituted pyrroles was studied on a sea urchin embryo model. Pyrroles unsubstituted at positions 2 and 5 were the most active. The activity increased with the number of methoxy groups in the Ar substituent. [ABSTRACT FROM AUTHOR]

Copyright of Phytothérapie is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Utilization of herbs for medicinal purpose started in the early history of mankind several thousand years ago. In this study, some plants that are used for lowering cholesterol level in local areas of Pakistan, such as Artemisia absinthium L., Swertia chirayita and Sphaeranthus indicus were screened for their phytochemical and antibacterial properties. For this purpose, these plants were extracted in different solvents i.e. ethanol, hexane and ethyl acetate. Phytochemcial analysis unveiled the existence of different bioactive compounds in these extracts. Presence of sugars was further confirmed by performing TLC. Antibacterial activity was determined against indicated bacterial strains, among all extracts Gul-e-mundi had maximum inhibition zone (23mm). DPPH free radical assay revealed the significant antioxidative potential of all the extracts where Gul-e-mundi showed maximum potential i.e., 83%. Plant extracts were also showing anti-proliferative activity on root tips of Allium cepa and Gul-e-mundi was observed to have maximum antimitotic activity i.e. 5%. GC-MS analysis revealed that oleic acid and linoleic acid were the compounds responsible for imparting antibacterial potential to Gul-e-mundi. In conclusion, among all the tested extracts Gul-e-mundi had maximum antibacterial, antioxidative and antimitotic potential. For future studies, phytochemcials responsible for these activities can be isolated and modified for pharmacological purpose. [ABSTRACT FROM AUTHOR]

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n-hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum. Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections. [ABSTRACT FROM AUTHOR]

A new series of benzothiazole amide derivatives ( 9a- l) were synthesized and characterized by Fourier-transform infrared (FT-IR), mass, and H and C nuclear magnetic resonance (NMR) spectroscopic techniques. The antimitotic activity of the newly synthesized compounds was determined by the Allium assay method, from which mitotic index values were calculated. Here, 9g (14.0 %) and 9l (14.5 %) showed mitotic index values most comparable to that of standard drug (14.4 %), while the remaining compounds showed lower mitotic index values; hence, these compounds inhibit the regular cell division process and are the most promising antimitotic agents. Based on the structural activity relationship, the maximum percentage inhibition was observed for compounds containing electron-withdrawing group, revealing enhanced antimitotic activity, while compounds with electron-donating groups such as furan ( 9g) and methyl ( 9l) were comparable to standard. The newly synthesized compounds were also screened for antimicrobial activity, with some of them showing remarkable activity. Graphical Abstract: [ABSTRACT FROM AUTHOR]

We previously reported that the IL-2 Luc LTT can detect immunosuppressive effects of drugs that are attributed to their antimitotic activity. Here, we report an official validation study of the IL-2 Luc LTT. In the Phase I study that evaluated five coded chemicals, the within-laboratory reproducibility of three independent laboratories was 100.0%. In the combined results of the Phase I and II studies that evaluated 20 coded chemicals, the between-laboratory reproducibility was 92.0%. When compared with the reference data based on the previously-reported immunotoxicological information, the predictivity of the combined Phase I and II studies was 76.0% for Lab A and 72.0% for Labs B and C. In contrast, in the study in which the lead laboratory examined 37 non-pharmaceutical chemicals, the predictivity of the IL-2 Luc LTT and the IL-2 Luc assay was 48.6% and 64.9%, respectively, whereas that of the combined assays was 74.3%. It is clear that an integrated approach combining multiple assays is necessary for the development of in vitro immunosuppression testing. These data suggest that the IL-2 Luc LTT alone is not sufficient as a component of the integrated approach, but the combination of the IL-2 Luc assay and IL-2 Luc LTT is promising. • The IL-2 Luc LTT is reproducible both between and within laboratories. • Neither the IL-2 Luc LTT or the IL-2 Luc assay provides satisfactory performance as an in vitro immunosuppression test. • The combination of these two assays resulted in significantly improved sensitivity and predictivity. • The IL-2 Luc LTT in addition to the IL-2 Luc assay is an indispensable component for the IATA of immunotoxicity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Triazole-Based Estradiol dimers inhibit tubulin assembly in vitro. • Triazole-Based Estradiol dimers reversibly disrupt microtubule structures in U2OS cells. • Triazole-Based Estradiol dimers show cytotoxic activities on cancer cell lines, arrest cells in the G2/M phase of the cell cycle and attenuate DNA/RNA synthesis. • Structural changes in the bridge are essential for the activity of estradiol dimers at the cytoskeletal level. • Simple linkers seem more suitable than more complex ones, bulky groups (benzyl pendants), are reducing the activity. Microtubule dynamic is exceptionally sensitive to modulation by small-molecule ligands. Our previous work presented the preparation of microtubule-targeting estradiol dimer (ED) with anticancer activity. In the present study, we explore the effect of selected linkers on the biological activity of the dimer. The linkers were designed as five-atom chains with carbon, nitrogen or oxygen in their centre. In addition, the central nitrogen was modified by a benzyl group with hydroxy or methoxy substituents and one derivative possessed an extended linker length. Thirteen new dimers were subjected to cytotoxicity assay and cell cycle profiling. Dimers containing linker with benzyl moiety substituted with one or more methoxy groups and longer branched ones were found inactive, whereas other structures had comparable efficacy as the original ED (e.g. D1 with IC 50 = 1.53 µM). Cell cycle analysis and immunofluorescence proved the interference of dimers with microtubule assembly and mitosis. The proposed in silico model and calculated binding free energy by the MM-PBSA method were closely correlated with in vitro tubulin assembly assay. [ABSTRACT FROM AUTHOR]

A novel series of 4-oxo- N-(4-hydroxyphenyl) retinamide (4-oxo-4- HPR) derivatives were synthesized with the aim of increasing the poor solubility of the parent compound in biological fluids, while maintaining the cytotoxic activity and the dual mechanism of action. The most promising compound 13a showed antiproliferative/apoptotic activity. The analysis of its mechanism of action revealed that it retained the particular characteristic of 4-oxo-4- HPR which is able to induce cell cycle arrest during the mitotic phase, coupled with the formation of aberrant mitotic spindles. [ABSTRACT FROM AUTHOR]

Alkoxy-substituted 1-aryl-3-(arylamino)prop-2-en-1-ones and 1-aryl-3-(arylamino)but-2en-1-ones were synthesized by the addition of anilines to 1,3-dioxo derivatives or aryl ethynyl ketones. The cis- trans isomerism of these compounds was studied. Biological tests on a sea urchin embryo model showed that 1-aryl-3-(arylamino)prop-2-en-1-ones exhibit an antimitotic effect both via microtubule destabilization and through the action on other cellular targets. The antiproliferative activity of these compounds increases with an increase in the number of alkoxy substituents in 1-aryl ring, whereas the presence of one methoxy group in the para position proved to be optimal for the arylamino moiety. [ABSTRACT FROM AUTHOR]

The pyrazole moiety containing analogs of podophyllotoxin as potential antimitotic agents were synthesized in five step reactions via chalcone route. The first step is the synthesis of chalcone (2a-d) by the reaction of substituted acetophenones with p-tolualdehyde in the presence of sodium hydroxide in water-ethanol mixture. The cyclopropyl ketones (3a-d) were prepared by the reaction of chalcones (2a-d) with trimethylsulfoxonium iodide (TMSOI) in dry DMSO. The key intermediate tetralones (4a-d) were prepared by the intramolecular cyclization reaction of cyclopropyl ketones (3a-d) in the presence of anhyd. stannic chloride and acetic anhydride in dry dichloromethane. These compounds (4a-d) on formylation give substituted hydroxylmethylene tetralones (5a-d). Further, pyrazole moiety containing analogs of podophyllotoxin (6a-d) were synthesized in high yields by the condensation of hydroxylmethylene tetralones (5a-d) with hydrazine hydrate in absolute ethanol. The structures of the synthesized compounds were confirmed by spectral and elemental analysis data. The synthesized compounds were also screened for their antimitotic activity. It is noteworthy that compounds 6d possessed excellent antimitotic activity, 6b and 6c showed considerable activity, and remaining 6a possessed least activity. Compound 6d was immense to show high antibacterial and antifungal activity against all bacterial and fungal strains compared with standard chloramphenicol and nystatin, respectively. [ABSTRACT FROM AUTHOR]

The pyrazole analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability of the chemicals. Initially, benzylideneacetophenones (chalcones) were prepared in high yields by Claisen-Schmidt reaction of acetophenones with 4-(methylthio)benzaldehyde. The cyclopropyl ketones were prepared in good yields by the reaction of chalcones with trimethylsulfoxonium iodide. Tetralones were prepared in good yields by the Friedel-Craft's intramolecular cyclization reaction of cyclopropyle ketones in the presence of anhyd. stannic chloride and acetic anhydride. The tetralones on formylation to give substituted hydroxylmethylene tetralones. Condensation of substituted hydroxylmethylene tetralones with hydrazine hydrate afforded target compounds. The structures of the synthesized compounds were confirmed by IR, H NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities. Among the synthesized compounds cyclopropyl ketones and pyrazole analogues of podophyllotoxin, compound 7-(methylthio)-5-(4-(methylthio)phenyl)-4,5-dihydro- H-benzo[g]indazole is more active than 5-(4-(methylthio)phenyl)-4,5-dihydro- H-benzo[g]indazole, 7-methyl-5-(4-(methylthio)phenyl)-4,5-dihydro- H-benzo[g]indazole, 7-methoxy-5-(4-(methylthio)phenyl)-4,5-dihydro- H-benzo[g]indazole and the key intermediate tetralones in 100, 200 and 400 ppm at 12, 18 and 24 h and also showed very good activity against screened bacteria and fungi compared to their standard. [ABSTRACT FROM AUTHOR]

Abstract: A new series of pyrrolo[3,4-h]quinazolines was conveniently prepared with a broad substitution pattern. A large number of derivatives was obtained and the cellular cytotoxicity was evaluated in vitro against 5 different human tumor cell lines with GI50 values reaching the low micromolar level (1.3–19.8 μM). These compounds were able to induce cell death mainly by apoptosis through a mitochondrial dependent pathway. Selected compounds showed antimitotic activity and a reduction of tubulin polymerization in a concentration-dependent manner. Moreover, they showed anti-angiogenic properties since reduced in vitro endothelial cell migration and disrupted HUVEC capillary-like tube network in Matrigel. [Copyright &y& Elsevier]

Polyalkoxy-5-(4-hydroxyphenyl)-3-phenyl-1,2,4-oxadiazoles were prepared from allylpolyalkoxybenzenes, the main metabolites of parsley and dill seeds. Due to the spatial arrangement of the aryl substituents provided by 1,2,4-oxadiozole fragment, these compounds can be considered as structural analogs of natural antimitotic combretastatins. The antimitotic activity of the synthesized compounds was evaluated in vivo using sea urchin embryo test. [ABSTRACT FROM AUTHOR]

Antimitotic agents prevent the mitosis process of cell cycle and are generally used for the treatment of cancer with good clinical success. QSAR analysis was performed on 33 reported 2-phenylindole-3-carbaldehyde derivatives to find out the structural requirements of these compounds for higher antimitotic activity. The dataset was divided into test set and training set by k-MCA. Factor analysis-stepwise multiple linear regression (FA-sMLR) method was used to develop statistically significant QSAR equations. QSAR analysis showed importance of topological indices like RTSA indices, structural information content indices, Balaban-type index from van der Waals weighted distance matrix Jhetv, rotatable bond fraction RBF, and Lovasz–Pelikan index LP1 on biological activity. The study also shows significance of electrostatic potential charges of different atoms as well as principal moment of inertia along Y axis and number of nitrogen atoms toward antimitotic activity of these compounds. [ABSTRACT FROM AUTHOR]

Silver nanoparticles synthesized using plant extracts as reducing and capping agents showed various biological activities. In the present study, colloidal silver nanoparticle solutions were produced from the aqueous extracts of Picea abies and Pinus nigra bark. The phenolic profile of bark extracts was analyzed by liquid chromatography coupled to mass spectrometry. The synthesis of silver nanoparticles was monitored using UV-Vis spectroscopy by measuring the Surface Plasmon Resonance band. Silver nanoparticles were characterized by attenuated total reflection Fourier transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, scanning electron microscopy, energy dispersive X-ray and transmission electron microscopy analyses. The antimicrobial and cytogenotoxic effects of silver nanoparticles were evaluated by disk diffusion and Allium cepa assays, respectively. Picea abies and Pinus nigra bark extract derived silver nanoparticles were spherical (mean hydrodynamic diameters of 78.48 and 77.66 nm, respectively) and well dispersed, having a narrow particle size distribution (polydispersity index values of 0.334 and 0.224, respectively) and good stability (zeta potential values of −10.8 and −14.6 mV, respectively). Silver nanoparticles showed stronger antibacterial, antifungal, and antimitotic effects than the bark extracts used for their synthesis. Silver nanoparticles obtained in the present study are promising candidates for the development of novel formulations with various therapeutic applications. [ABSTRACT FROM AUTHOR]

Abstract: The syntheses and antimitotic activity of several novel analogs of 2-methoxyestradiol are described. Structural modifications include ring-D homologation, aromatization of the six-membered ring-D to a chrysine type molecule, and introduction of unsaturation in five-membered ring-D along with substitution of alkyl and ethynyl groups for the 17β-hydroxy function. Of nine analogs synthesized, five have demonstrated superior antiproliferative activities compared to 2-methoxyestradiol. [Copyright &y& Elsevier]

Abstract: Eight stilbenoids, 1-(p-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (1), 2,7-dihydroxy-1,3-bis(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene (2), 4,7-dihydroxy-1-(p-hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene (3), 3,3′-dihydroxy-2′,6′-bis(p-hydroxybenzyl)-5-methoxybibenzyl (4), 3′,5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (5), blestriarenes B (6) and C (7), and blestrianol A (8) have been isolated by the guidance of inhibitory effect of tubulin polymerization from the tubers of Bletilla striata (Orchidaceae). Among them, both of bisbenzyls 4 and 5 inhibited the polymerization of tubulin at IC50 10μM, respectively. Furthermore bisbenzyl 4 potentiated the cytotoxicity of SN-38 in BCRP-transduced K562 (K562/BCRP) cells. [Copyright &y& Elsevier]

Two new coumarins, glaumacidines A (1) and B (2), and the related coumarins (3–7) have been isolated from the rhizomes of Glaucidium palmatum (Glaucidiaceae). The absolute configurations of 1 and 2 and trans- and cis-glaupadiols (3 and 4, respectively) were elucidated by spectroscopic data, chemical derivatization, and exciton chirality method. Glaupalol (5) enhanced the polymerization of tubulin and affected synergistically with paclitaxel on inhibition of KB cell proliferation. [Copyright &y& Elsevier]

The syntheses and antimitotic activity of several novel 2-methoxyestradiol analogs are described. Structural modifications investigated include introduction of additional unsaturation in rings B and D; inversion at C-13; and substitution at the C-2, C-15, C-16, and C-7α positions. Of 15 analogs synthesized, 2 have demonstrated superior biological activities compared to 2-methoxyestradiol. [Copyright &y& Elsevier]

Various 5-chloroarylidene-2-amino substituted derivatives of imidazoline-4-one were synthesized and evaluated for their activity in vitro against Mycobacterium tuberculosis and other type strains of bacteria and fungi. 2-Chloro- and 2,4-dichlorobenzylidene substituted hydantoins exhibited antimycobacterial effect. The most potent compounds 3i, 3j, 3o, 3q and 3s were classified for further tests. The antimitotic effect of the investigated hydantoins was also examined. [Copyright &y& Elsevier]

Silver nanoparticles synthesized using plant extracts as reducing and capping agents showed various biological activities. In the present study, colloidal silver nanoparticle solutions were produced from the aqueous extracts of Picea abies and Pinus nigra bark. The phenolic profile of bark extracts was analyzed by liquid chromatography coupled to mass spectrometry. The synthesis of silver nanoparticles was monitored using UV-Vis spectroscopy by measuring the Surface Plasmon Resonance band. Silver nanoparticles were characterized by attenuated total reflection Fourier transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, scanning electron microscopy, energy dispersive X-ray and transmission electron microscopy analyses. The antimicrobial and cytogenotoxic effects of silver nanoparticles were evaluated by disk diffusion and Allium cepa assays, respectively. Picea abies and Pinus nigra bark extract derived silver nanoparticles were spherical (mean hydrodynamic diameters of 78.48 and 77.66 nm, respectively) and well dispersed, having a narrow particle size distribution (polydispersity index values of 0.334 and 0.224, respectively) and good stability (zeta potential values of -10.8 and -14.6 mV, respectively). Silver nanoparticles showed stronger antibacterial, antifungal, and antimitotic effects than the bark extracts used for their synthesis. Silver nanoparticles obtained in the present study are promising candidates for the development of novel formulations with various therapeutic applications.

Copyright of Protoplasma is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Conditioned medium (CM) obtained from rat cerebellar astrocytes cultured in a serumcontaining medium was able to inhibit [H]thymidine incorporation into proliferating astrocytes, when compared to fresh medium. This effect could be attributed to two fractions of the CM with different molecular weights. The low molecular weight fraction (M<1,000) inhibited the cellular transport of the labeled precursor, without significantly affecting cell proliferation. The high molecular weight fraction (M>10,000) showed a strong inhibitory effect on astrocyte proliferation, which was documented using different assay techniques: i) [H]thymidine incorporation performed in conditions preventing the effects of CM on transport; ii) [H]thymidine autoradiography; iii) determination of the DNA content of the cultures. The inhibitory activity was present in media conditioned by non proliferating astrocytes treated with the antimitotic cytosine arabinoside, but not in media conditioned by neuron-enriched cultures nor in a chemically defined (N2) CM. The antiproliferative activity of astrocyte CM could be due either to a rapid depletion of mitogenic factors present in serum, or, to a secretion of growth inhibitory factor(s) by cultured astrocytes. [ABSTRACT FROM AUTHOR]

Abstract: Lobaric acid (1) has been isolated from lichen, Stereocaulon sasakii together with a new benzofuran, sakisacaulon A (2). Lobaric acid (1) inhibited the polymerization of tubulin. Structure–activity relationship of lobaric acid and its derivatives on inhibitory activity of tubulin polymerization was discussed. [Copyright &y& Elsevier]

ABSTRACT: Medicinal plants are being used from prehistoric times for the curative purposes. In present study, local plants of Gilgit-Baltistan i.e., Cannabis sativa, Arteimisia sieversiana and Delphinium brunonianum were investigated for their antibacterial and antioxidant potential. Ethyl acetate extracts of these selected plants revealed the presence of different phytochemicals in all extracts. Maximum antibacterial activity against Bacillus(KC 881030) and Pseudomonas(KC 881031) strains was shown by C. sativa(14 mm). Its minimum inhibition concentration(MIC) was found to be 1.56 mg/ml against test strain of Bacillus. Free radical scavenging ability of C. sativa plant extract was highest(68.9%) as compared to rest of the tested extracts. Antimitotic assay showed considerable antimitotic potential(20% mitotic index) of C. sativa. Thin Layer Chromatography revealed 11 different spots that were further partially purified to determine their antibacterial activity. Significant zone of inhibition were exhibited by two spots i.e. 17 mm and 18 mm. In future, bioactive components of these selected plants can be used in pharmaceutical sector as antioxidant and antimitotic agents. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women worldwide. Estrogen receptor-positive (ER+) breast cancer represents approximately 75% of diagnosed cases, while 15-20% of them are triple-negative (TN). Although there have been improvements in the therapeutic approach, the mortality rate remains elevated. Thus, it is necessary to identify new chemotherapeutic agents. The present study aimed to evaluate the effects of calein C, a sesquiterpene lactone isolated from Calea pinnatifida , on breast cancer cell lines MCF-7 (ER+), Hs578T (TN) and MDA-MB-231 (TN). Calein C significantly reduced the viability of all cell lines; however, MCF-7 cells were more responsive than MDA-MB-231 or Hs578T cells. Thus, the MCF-7 cell line was selected for further investigation. We demonstrated that calein C inhibited cell cycle progression in MCF-7 cells at M-phase. Increased frequency of mitosis was observed in calein C-treated samples compared to the control group, especially of the cell population in initial stages of the mitosis. These events were associated with the ability of calein C to modulate expression levels of critical regulators of mitosis progression. We observed a significant reduction in the relative mRNA abundance of PLK1 and AURKB along with a concomitant increase in CDKN1A (p21) in treated samples. In addition, calein C induced apoptosis in MCF-7 cells due to, at least in part, its ability to reduce the BCL2/BAX ratio. Therefore, our data provide evidence that calein C is an important antimitotic agent and should be considered for further in vivo investigations.

Background: Phenstatin and their derivatives display remarkable antiproliferative activity toward a wide variety of preclinical tumor models. Structural simplicity and excellent stability of phenstatins offer a stimulating premise for developing various derivatives with profound antimitotic activity and excellent cytotoxicity., Objective: To do analysis of literature that phenstatins derivatives inhibit tubulin polymerization through their interaction at the colchicine binding site of microtubules and arrest the G2/M phase of the cell cycle. In addition, phenstatin derivatives are undergoing clinical evaluation as vascular targeting/disrupting agents and also exhibit direct antiangiogenic properties., Methods: An organised well designed and appropriately managed search of bibliographic databases for peer-reviewed research literature using a focused review question and inclusion/ exclusion criteria has been done for this article., Conclusion: In this review article, the synthesis and structure-activity relationships of phenstatin and a wide number of their reported analogues with modifications to ring A, ring B, and to the keto position are discussed in the perspective of medicinal chemistry with proper conclusion., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In our continuing study on a survey of biologically active natural products from heartwood of Santalum album (Southwest Indian origin), we newly found potent fish toxic activity of an n -hexane soluble extract upon primary screening using killifish (medaka) and characterized α-santalol and β-santalol as the active components. The toxicity (median tolerance limit (TLm) after 24 h at 1.9 ppm) of α-santalol was comparable with that of a positive control, inulavosin (TLm after 24 h at 1.3 ppm). These fish toxic compounds including inulavosin were also found to show a significant antifungal effect against a dermatophytic fungus, Trichophyton rubrum . Based on a similarity of the morphological change of the immobilized Trichophyton hyphae in scanning electron micrographs between treatments with α-santalol and griseofulvin (used as the positive control), inhibitory effect of α-santalol on mitosis (the antifungal mechanism proposed for griseofulvin) was assessed using sea urchin embryos. As a result, α-santalol was revealed to be a potent antimitotic agent induced by interference with microtubule assembly. These data suggested that α-santalol or sandalwood oil would be promising to further practically investigate as therapeutic agent for cancers as well as fungal skin infections., Competing Interests: The authors declare no conflict of interest.