Laminaria japonica cyclic peptides exert anti-colorectal carcinoma effects through apoptosis induction in vitro and in vivo.

Laminaria japonica is consumed as a health food and used as a traditional medicine because of its biochemical and pharmacological abilities. However, the anti-tumor effect of L. japonica peptides has not been well explored. In the current study, three novel L. japonica cyclic peptides (LCPs) were isolated using an anti-cancer activity tracking method. LCP-3 [cyclo-(Trp-Leu-His-Val)] significantly induced apoptosis in Caco-2 cells in vitro. LCP-3 increased the Bax/Bcl-2 ratio, activated caspases, and regulated the p53/murine double minute 2 network. LCP-3 blocked Caco-2 cells in G0/G1 phase, which was accompanied by the inhibition of cyclin expression. Furthermore, LCP-3 inhibited colon cancer growth and induced cancer cell apoptosis in tumor-bearing mice. Notably, LCP-3 might be a potential agent for the prevention of colon cancer.

Electric Assisted Salt-Responsive Bacterial Killing and Release of Polyzwitterionic Brushes in Low-Concentration Salt Solution.

Polyzwitterionic brushes with strong antipolyelectrolyte effects have shown great potential as versatile platforms for the development of switchable friction/lubrication and bacterial absorption/desorption surfaces. However, the surface property switches of these brushes are usually triggered by high salt concentrations (>0.53 M), thereby greatly limiting their applications in biological fields where the salt concentration for mammals is ?0.15 M. To solve this problem, an electric field was used to assist the salt-responsive process of the polyzwitterionic brushes to achieve bacterial release at low concentrations of the salt solution. Briefly, poly(3-(dimethyl (4-vinylbenzyl) ammonium) propyl sulfonate) (polyDVBAPS) brushes grafted on ITO surfaces were prepared by surface initiated atom transfer radical polymerization. The bacterial release of this surface was conducted under an electric field, where anions were migrated and enriched around the brush-grafted ITO surface as anode. The local high concentration ion led to the conformation change of the brush and release of the attached bacteria. The effect of salt type, salt concentration, electric field strength, and conducting time on the bacterial release properties were investigated. The results indicated that under an electrical field of 3 V/mm, polyDVBAPS showed release capacities of ?93% for E. coli and ?81% for S. aureus in 0.12 M NaCl electrolyte solution. Furthermore, by the introduction of a bactericidal agent, i.e., Triclosan (TCS), an antibacterial surface with dual functions of killing and release was fabricated. This surface could kill ?90% and release 95% of attached E. coli in a 0.12 M NaCl solution by the application of a 3 V/mm electric field. This work demonstrated the feasibility of triggering a salt-responsive behavior of polyzwitterionic at low salt concentration by assistance of electric field, which would greatly extend the applications of polyzwitterionic, in particular in biological applications.

Structural Dependence of Salt-Responsive Polyzwitterionic Brushes with an Anti-Polyelectrolyte Effect.

Some polyzwitterionic brushes exhibit a strong "anti-polyelectrolyte effect" and ionic specificity that make them versatile platforms to build smart surfaces for many applications. However, the structure-property relationship of zwitterionic polymer brushes still remains to be elucidated. Herein, we aim to study the structure-dependent relationship between different zwitterionic polymers and the anti-polyelectrolyte effect. To this end, a series of polyzwitterionic brushes with different cationic moieties (e.g., imidazolium, ammonium, and pyridinium) in their monomeric units and with different carbon spacer lengths (e.g., CSL = 1, 3, and 4) between the cation and anion were designed and synthesized to form polymer brushes via the surface-initiated atom transfer radical polymerization. All zwitterionic brushes were carefully characterized for their surface morphologies, compositions, wettability, and film thicknesses by atomic force microscopy, contact angle measurement, and ellipsometry, respectively. The salt-responsiveness of all zwitterionic brushes to surface hydration and friction was further examined and compared both in water and in salt solutions with different salt concentrations and counterion types. The collective data showed that zwitterionic brushes with different cationic moieties and shorter CSLs in salt solution induced higher surface friction and lower surface hydration than those in water, exhibiting strong anti-polyelectrolyte effect salt-responsive behaviors. By tuning the CSLs, cationic moieties, and salt concentrations and types, the surface wettability can be changed from a highly hydrophobic surface (∼60°) to a highly hydrophilic surface (∼9°), while interfacial friction can be changed from ultrahigh friction (µ ≈ 4.5) to superior lubrication (µ ≈ 10-3). This work provides important structural insights into how subtle structural changes in zwitterionic polymers can yield great changes in the salt-responsive properties at the interface, which could be used for the development of smart surfaces for different applications.

Salt-Induced Regenerative Surface for Bacteria Killing and Release.

Antibacterial surfaces with both bacteria killing and release functions show great promise in biological and biomedical applications, in particular for reusable medical devices. However, these surfaces either require a sophisticated technique to create delicate structures or need rigorous stimuli to trigger the functions, greatly limiting their practical application. In this study, we made a step forward by developing a simple system based on a salt-responsive polyzwitterionic brush. Specifically, the salt-responsive brush of poly(3-(dimethyl (4-vinylbenzyl) ammonium) propyl sulfonate) (polyDVBAPS) was endowed with bactericidal function by grafting an effective bactericide, i.e., triclosan (TCS). This simple functionalization successfully integrated the bacteria attach/release function of polyDVBAPS and bactericidal function of TCS. As a result, the surface could kill more than 95% attached bacteria and, subsequently, could rapidly detach ∼97% bacteria after gently shaking in 1.0 M NaCl for 10 min. More importantly, such high killing efficiency and release rate could be well retained (unchanged effectiveness of both killing and release after four severe killing/release cycles), indicating the highly efficient regeneration and long-term reusability of this system. This study not only contributes zwitterionic polymers by conferring new functions but also provides a new, highly efficient and reliable surface for "killing-release" antibacterial strategy.

Salt-Responsive Zwitterionic Polymer Brushes with Tunable Friction and Antifouling Properties.

Development of smart, multifunction materials is challenging but important for many fundamental and industrial applications. Here, we synthesized and characterized zwitterionic poly(3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl)propane-1-sulfonate) (polyVBIPS) brushes as ion-responsive smart surfaces via the surface-initiated atom transfer radical polymerization. PolyVBIPS brushes were carefully characterized for their surface morphologies, compositions, wettability, and film thicknesses by atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), contact angle, and ellipsometer, respectively. Salt-responsive, switching properties of polyVBIPS brushes on surface hydration, friction, and antifouling properties were further examined and compared both in water and in salt solutions with different salt concentrations and counterion types. Collective data showed that polyVBIPS brushes exhibited reversible surface wettability switching between in water and saturated NaCl solution. PolyVBIPS brushes in water induced the larger protein absorption, higher surface friction, and lower surface hydration than those in salt solutions, exhibiting "anti-polyelectrolyte effect" salt responsive behaviors. At appropriate ionic conditions, polyVBIPs brushes were able to switch to superlow fouling surfaces (<0.3 ng/cm(2) protein adsorption) and superlow friction surfaces (u ∼ 10(-3)). The relationship between brush structure and its salt-responsive performance was also discussed. This work provides new zwitterionic surface-responsive materials with controllable antifouling and friction capabilities for multifunctional applications.

An Anisotropic Hydrogel by Programmable Ionic Crosslinking for Sequential Two-Stage Actuation under Single Stimulus.

As one of the most important anisotropic intelligent materials, bi-layer stimuli-responsive actuating hydrogels have proven their wide potential in soft robots, artificial muscles, biosensors, and drug delivery. However, they can commonly provide a simple one-actuating process under one external stimulus, which severely limits their further application. Herein, we have developed a new anisotropic hydrogel actuator by local ionic crosslinking on the poly(acrylic acid) (PAA) hydrogel layer of the bi-layer hydrogel for sequential two-stage bending under a single stimulus. Under pH = 13, ionic-crosslinked PAA networks undergo shrinking (-COO-/Fe3+ complexation) and swelling (water absorption) processes. As a combination of Fe3+ crosslinked PAA hydrogel (PAA@Fe3+) with non-swelling poly(3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl)propane-1-sulfonate) (PZ) hydrogel, the as-prepared PZ-PAA@Fe3+ bi-layer hydrogel exhibits distinct fast and large-amplitude bidirectional bending behavior. Such sequential two-stage actuation, including bending orientation, angle, and velocity, can be controlled by pH, temperature, hydrogel thickness, and Fe3+ concentration. Furthermore, hand-patterning Fe3+ to crosslink with PAA enables us to achieve various complex 2D and 3D shape transformations. Our work provides a new bi-layer hydrogel system that performs sequential two-stage bending without switching external stimuli, which will inspire the design of programmable and versatile hydrogel-based actuators.

Versatile and Simple Strategy for Preparing Bilayer Hydrogels with Janus Characteristics.

Bilayer hydrogels are attracting tremendous attention for their capability to integrate several different functions on the two sides of the gel, that is, imparting the gel with Janus characteristics, which is highly desired in many engineering and biomedical applications including soft actuators, hydrogel patches, and wearable electronics. However, the preparation process of the bilayer materials usually involves several complicated steps and is time-consuming, while the interfacial bonding is another main concern. Here, a simple and versatile method is proposed to obtain bilayer hydrogels within just one step based on the method of introducing viscosity contrast of the precursors for different layers. The bilayer structure can be well maintained during the whole preparation process with a constrained interfacial molecular exchange to ensure the strong bonding strength. The key requirements for forming distinct bilayer structures in situ are studied and discussed in detail. Bilayer hydrogels with different chemical designs are prepared via this strategy to tailor the good distribution of desired functions for soft actuators, wound healing patches, and wearable electronics. We believe that the strategy illustrated here will provide new insights into the preparation and application of bilayer materials.

Micro- and macroscopically structured zwitterionic polymers with ultralow fouling property.

HYPOTHESIS: Polyzwitterions as a promising class of materials are often used to construct antifouling surfaces with optimized conformation and compositions for a wide variety of antifouling applications. While numerous zwitterionic polymers have been identified for their antifouling capacity, the exact relationship among molecular structure, surface hydration property, and antifouling performance of zwitterionic polymers at different scales still remains elusive. EXPERIMENTS: we first designed and synthesized a new zwitterionic monomer of 3-(4-(methacryloyloxy)-1-methylpiperidin-1-ium-1-yl)-propane-1-sulfonate (MAMPS), then used MAMPS monomers to fabricate into homogenous polymer brushes on Au substrate using SI-ATRP and heterogeneous double-network (DN) hydrogels combining with Agar network via one-pot, heating-cooling-photopolymerization method, and finally evaluated their antifouling ability to resist the adsorption of protein/cell/bacteria on the two different polymer forms at microscopic and macroscopic scales. FINDINGS: For microscopic polyMAMPS brushes, they exhibited excellent resistance to nonspecific protein adsorption from both undiluted blood serum/plasma (0.3-5 ng/cm2), cell adhesion up to 3 days, and clinically relevant bacterial attachment for 72 h at the optimal film thicknesses of 20-40 nm. For macroscopic Agar/polyMAMPS DN hydrogels, they also exhibited approximately 96% less protein adhesion than tissue culture polystyrene (TCPS). Different structured materials consisting of polyMAMPS at both micro- and macro-scales demonstrate its excellent, intrinsic antifouling property, which could be related to their highly water binding character of zwitterionic groups. PolyMAMPS materials, alternative to commonly used poly(sulfobetaine methacrylate) (polySBMA) and poly(carboxybetaine methacrylate) (polyCBMA) zwitterions, hold great promise for antifouling designs and applications.

Retracted Article: Structural characterization of ginseng cyclopeptides and detection of capability to induce apoptosis in gastrointestinal cancer cells.

Gastrointestinal tumors are the most frequently diagnosed malignancy and the second highest contributor to cancer mortality. Cyclopeptides are rarely isolated from ginseng because they are often present at low concentrations in a complex matrix. In the current study, seven novel ginseng cyclopeptides (GCPs) were isolated and their anti-tumor potency was explored. Anti-proliferative test results show that the (GCP-1)∼[cyclo-(L-Trp-L-Glu-L-Phe-L-Thr)] peptide display the best anti-proliferative activity in gastric cancer SGC-7901 cells in vitro, with an IC50 value of 37.8 ± 3.13 µM. Flow cytometry analysis shows that GCP-1 (7.56-189 µM) clearly induce early apoptosis and mitochondrial membrane potential collapse, and block the cells at the G0/G1 phase. A further study revealed that GCP-1 induces apoptosis by activating the caspases, suppressing the thioredoxin (Trx) system and subsequently activating a number of Trx-dependent pathways, including those involving apoptotic signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinases (MAPKs). The cyclopeptides in ginseng are an important resource for the research and development of anti-neoplastic drugs.

Super Hydrophilic Semi-IPN Fluorescent Poly(N-(2-hydroxyethyl)acrylamide) Hydrogel for Ultrafast, Selective, and Long-Term Effective Mercury(II) Detection in a Bacteria-Laden System.

Convenient, low-cost chemosensors for hazardous mercury ion detection have been receiving more and more attention in recent studies. However, most of these practical studies are based on an ideal sterile detecting atmosphere and ignore the role of bacteria in actual Hg(II) analytes. Herein, we demonstrate a new type of hydrophilic semi-IPN fluorescent polyHEAA hydrogel chemosensors fabricated by UV polymerization in situ interpenetrating fluorescent polymer PA-NDBCB with a polyHEAA network. Because of specific intermolecular interaction, i.e., hydrogen bonding between hydrophilic fluorescent polymer and polyHEAA matrix comprising a distinct semi-IPN structure, the mechanical property of bulk fluorescent hydrogels can be greatly improved over that of pure polyHEAA hydrogels. Moreover, the design of the hydrogel chemosensors rely on the highly efficient cyclization reaction between Hg(II) ions and the thiourea moieties that induce a visible "green-to-blue" fluorescence color change. On account of the hydrophilic porous structures, these hydrogel chemosensors achieve ultrafast, sensitive, selective Hg(II) detection (detection limit of 0.067 µM) and enable facile ratiometric actual detection in real-world aqueous system. Notably, they maintain fluorescence emission and detection property even under long-term coculture in a complex E. coli bacteria-laden environment. This novel strategy could inspire future construction of soft interfaces/fluorescent apparatus for hazardous Hg(II) detection in a complex real-world system.

One-Pot and One-Step Fabrication of Salt-Responsive Bilayer Hydrogels with 2D and 3D Shape Transformations.

Bilayer hydrogels are one of the most promising materials for use as soft actuators, artificial muscles, and soft robotic elements. Therefore, the development of new and simple methods for the fabrication of such hydrogels is of particular importance for both academic research and industrial applications. Herein, a facile, one-pot, and one-step methodology was used to prepare bilayer hydrogels. Specifically, several common monomers, including N-isopropyl acrylamide, acrylamide, and N-(2-hydroxyethyl)acrylamide, as well as two salt-responsive zwitterionic monomers, 3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (VBIPS) and dimethyl-(4-vinylphenyl)ammonium propane sulfonate (DVBAPS), were chosen and employed with different combinations and ratios to understand the formation and structural tunability of the bilayer hydrogels. The results indicated that a salt-responsive zwitterionic-enriched copolymer, which could precipitate from water, plays a dominant role in the formation of the bilayer structure and that the ratio between the common monomer and the zwitterionic monomer had a significant effect on the structure. Due to the salt-responsive properties of polyVBIPS and polyDVBAPS, the resultant bilayer hydrogels exhibited excellent bidirectional bending properties in response to the salt solution. With the optimal monomer pair and ratio determined, the bend of the hydrogel could be reversed from ∼-360 to ∼266° in response to a switch between water and a 1.0 M NaCl solution. Additionally, this method was further used to fabricate small-scaled patterns with structural and compositional distinction in two-dimensional hydrogel sheets. These two-dimensional hydrogel sheets exhibited complex and reversible three-dimensional shape transformations due to the different bending behaviors of the patterned hydrogel stripes under the action of an external stimulus. This work provides greater insight into the mechanism of the one-step, one-pot method fabrication of bilayer hydrogels, demonstrates the ability of this method for the preparation of small-scale patterns in hydrogel sheets to endow the complex with a three-dimensional shape transformation capability, and hopefully opens up a new pathway for the design and fabrication of smart hydrogels.

Design of salt-responsive and regenerative antibacterial polymer brushes with integrated bacterial resistance, killing, and release properties.

The development of smart materials and surfaces with multiple antibacterial actions is of great importance for both fundamental research and practical applications, but this has proved to be extremely challenging. In this work, we proposed to integrate salt-responsive polyDVBAPS (poly(3-(dimethyl(4-vinylbenzyl) ammonio)propyl sulfonate)), antifouling polyHEAA (poly(N-hydroxyethyl acrylamide)), and bactericidal TCS (triclosan) into single surfaces by polymerizing and grafting polyDVBAPS and polyHEAA onto the substrate in a different way to form two types of polyDVBAPS/poly(HEAA-g-TCS) and poly(DVBAPS-b-HEAA-g-TCS) brushes with different hierarchical structures, as confirmed by X-ray photoelectron spectroscopy (XPS), atom force microscopy (AFM), and ellipsometry. Both types of polymer brushes demonstrated their tri-functional antibacterial activity to resist bacterial attachment by polyHEAA, to release ∼90% of dead bacteria from the surface by polyDVBAPS, and to kill ∼90% of bacteria on the surface by TCS. Comparative studies also showed that removal of any component from polyDVBAPS/poly(HEAA-g-TCS) and poly(DVBAPS-b-HEAA-g-TCS) compromised the overall antibacterial performance, further supporting a synergistic effect of the three compatible components. More importantly, the presence of salt-responsive polyDVBAPS allowed both brushes to regenerate with almost unaffected antibacterial capacity for reuse in multiple kill-and-release cycles. The tri-functional antibacterial surfaces present a promising design strategy for further developing next-generation antibacterial materials and coatings for antibacterial applications.

Preparation of carbon-based hybrid particles and their application in microcellular foaming and flame-retardant materials.

Polymeric microcellular foams with high strength and light weight are very important for industrial applications. However, regulating their cell structure and their weak flame retardancy are problematic. We designed single-arm POSS-based ionic liquids ([bel-POSS][PF6]), and constructed hybrid composites based on physical interaction between ionic liquids and carbon-based materials in PS microcellular foaming. Ionization of bel-POSS could result in a quaternary ammonium reaction and ion-exchange reaction, and the carbon materials exhibit good dispersion through blending. The prepared hybrid composites showed high CO2 adsorption. Conical calorimeter tests showed that PS composite materials could reduce the heat release rate, total heat release, toxic gases (CO2 and CO) release, and amount of smoke generated. These carbon materials could affect PS micropore structure, including the cell diameter and density. Upon addition of 5 wt% of carbon materials, the hole diameter decreased by >50%, and the hole density increased nearly ten folds.

Dual Salt- and Thermoresponsive Programmable Bilayer Hydrogel Actuators with Pseudo-Interpenetrating Double-Network Structures.

Development of smart soft actuators is highly important for fundamental research and industrial applications but has proved to be extremely challenging. In this work, we present a facile, one-pot, one-step method to prepare dual-responsive bilayer hydrogels, consisting of a thermoresponsive poly( N-isopropylacrylamide) (polyNIPAM) layer and a salt-responsive poly(3-(1-(4-vinylbenzyl)-1 H-imidazol-3-ium-3-yl)propane-1-sulfonate) (polyVBIPS) layer. Both polyNIPAM and polyVBIPS layers exhibit a completely opposite swelling/shrinking behavior, where polyNIPAM shrinks (swells) but polyVBIPS swells (shrinks) in salt solution (water) or at high (low) temperatures. By tuning NIPAM:VBIPS ratios, the resulting polyNIPAM/polyVBIPS bilayer hydrogels enable us to achieve fast and large-amplitude bidirectional bending in response to temperatures, salt concentrations, and salt types. Such bidirectional bending, bending orientation, and degree can be reversibly, repeatedly, and precisely controlled by salt- or temperature-induced cooperative swelling-shrinking properties from both layers. Based on their fast, reversible, and bidirectional bending behavior, we further design two conceptual hybrid hydrogel actuators, serving as a six-arm gripper to capture, transport, and release an object and an electrical circuit switch to turn on-and-off a lamp. Different from the conventional two- or multistep methods for preparation of bilayer hydrogels, our simple, one-pot, one-step method and a new bilayer hydrogel system provide an innovative concept to explore new hydrogel-based actuators through combining different responsive materials that allow us to program different stimuli for soft and intelligent materials applications.

Salt-Responsive Bilayer Hydrogels with Pseudo-Double-Network Structure Actuated by Polyelectrolyte and Antipolyelectrolyte Effects.

Development of stimuli-responsive, shape-transformable materials is fundamentally and practically important for smart actuators. Herein, we design and synthesize a bilayer hydrogel by assembling a polycationic (polyMETAC/HEAA) layer with polyelectrolyte effect and a polyzwitterionic (polyVBIPS) layer with antipolyelectrolyte effect together. The bilayer hydrogels adopt a pseudo-double-network structure, and both polyelectrolyte and polyzwitterionic layers have salt-responsive swelling and shrinkage properties, but in a completely opposite way. The resulting polyMETAC/HEAA-polyVBIPS bilayer hydrogels exhibit bidirectional bending in response to salt solutions, salt concentrations, and counterion types. Such bidirectional bending of this bilayer hydrogel is fully reversible and triggered between salt solution and pure water multiple times. The bending orientation and degree of the bilayer hydrogel is driven by the opposite volume changes between the volume shrinking (swelling) of polyMETAC/HEAA layer and the volume swelling (shrinking) of polyVBIPS layer. Such cooperative, not competitive, salt-responsive swelling-shrinking properties of the two layers are contributed to by the polyelectrolyte and antipolyelectrolyte effects from the respective layers. Moreover, an eight-arm gripper made of this bilayer hydrogel is fabricated and demonstrates its ability to grasp an object in salt solution and release the object in water. This work provides a new shape-regulated, stimuli-responsive asymmetric hydrogel for actuator-based applications.

Salt-responsive polyzwitterionic materials for surface regeneration between switchable fouling and antifouling properties.

UNLABELLED: Development of smart regenerative surface is a highly challenging but important task for many scientific and industrial applications. Specifically, very limited research efforts were made for surface regeneration between bio-adhesion and antifouling properties, because bioadhesion and antifouling are the two highly desirable but completely opposite properties of materials. Herein, we developed salt-responsive polymer brushes of poly(3-(1-(4-vinylbenzyl)-1H-imidazol-3-ium-3-yl) propane-1-sulfonate) (polyVBIPS), which can be switched reversibly and repeatedly between protein capture/release and surface wettability in a controllable manner. PolyVBIPS brush has demonstrated its switching ability to resist both protein adsorption from 100% blood plasma/serum and bacterial attachment in multiple cycles. PolyVBIPS brush also exhibits reversible surface wettability from ∼40° to 25° between in PBS and in 1M NaCl solutions in multiple cycles. Overall, the salt-responsive behaviors of polyVBIPS brushes can be interpreted by the "anti-polyelectrolyte effect", i.e. polyVBIPS brushes adopt a collapsed chain conformation at low ionic strengths to achieve surface adhesive, but an extended chain conformation at high ionic strength to realize antifouling properties. We expect that polyVBIPS will provide a simple, robust, and promising system for the fabrication of smart surfaces with biocompatible, reliable, and regenerative properties. STATEMENT OF SIGNIFICANCE: Unlike many materials with "one-time switching" capability for surface regeneration, we developed a new regenerative surface of zwitterionic polymer brush, which exhibits a reversible salt-induced switching property between a biomolecule-adhesive state and a biomolecule repellent state in complex media for multiple cycles. PolyVBIPS is easily synthesized and can be straightforward coated on the surface, which provides a simple, robust, and promising system for the fabrication of smart surfaces with biocompatible, reliable, regenerative properties.

Elaboration of thorough simplified vinca alkaloids as antimitotic agents based on pharmacophore similarity.

Thorough simplification of vinca alkaloids based on pharmacophore similarity has been conducted. A concise process for the syntheses of target compounds was successfully developed with yields from poor to excellent (19-98%). Cell growth inhibitory activities of these synthesized compounds were evaluated in five cancer cell lines including MCF-7, MDA-MB-231, HepG2, HepG2/ADM and K562. Almost all compounds exhibited moderate antitumor activity with optimal IC50 value of 0.89 ± 0.07 µM in MCF-7 cells. Investigation of structure-activity relationship (SAR) indicates that electron-withdraw substituents on the ring contribute to the enhancement of the antitumor activities. The simplified vinca alkaloids are confirmed as antimitotic agents, which inhibit the polymerization of tubulin just like vinblastine.