Sustainable carbonaceous nanomaterial supported palladium as an efficient ligand-free heterogeneouscatalyst for Suzuki-Miyaura coupling.

A novel ligand-free heterogeneous catalyst was synthesized via pyrolysis of Samanea saman pods to produce carbon nanospheres (SS-CNSs), which served as a carbon support for immobilizing palladium nanoparticles through an in situ reduction technique (Pd/SS-CNS). The SS-CNSs effectively integrated 3% of Pd on their surfaces with no additional activation procedures needed. The nanomaterials obtained underwent thorough characterization employing various techniques such as FT-IR, XRD, FE-SEM, TEM, EDS, ICP-AES, and BET. Subsequently, the efficiency of this Pd/SS-CNS catalyst was assessed for the synthesis of biaryl derivatives via Suzuki coupling, wherein different boronic acids were coupled with various aryl halides using an environmentally benign solvent mixture of EtOH/H2O and employing only 0.1 mol% of Pd/SS-CNS. The catalytic system was conveniently recovered through centrifugation and demonstrated reusability without any noticeable decline in catalytic activity. This approach offers economic viability, ecological compatibility, scalability, and has the potential to serve as an alternative to homogeneous catalysis.

Small Molecule Optical Probes for Detection of H2S in Water Samples: A Review.

Hydrogen sulfide (H2S) is closely linked to not only environmental hazards, but also it affects human health due to its toxic nature and the exposure risks associated with several occupational settings. Therefore, detection of this pollutant in water sources has garnered immense importance in the analytical research arena. Several research groups have devoted great efforts to explore the selective as well as sensitive methods to detect H2S concentrations in water. Recent studies describe different strategies for sensing this ubiquitous gas in real-life water samples. Though many of the designed and developed H2S detection approaches based on the use of organic small molecules facilitate qualitative/quantitative detection of the toxic contaminant in water, optical detection has been acknowledged as one of the best, attributed to the simple, highly sensitive, selective, and good repeatability features of the technique. Therefore, this review is an attempt to offer a general perspective of easy-to-use and fast response optical detection techniques for H2S, fluorimetry and colorimetry, over a wide variety of other instrumental platforms. The review affords a concise summary of the various design strategies adopted by various researchers in constructing small organic molecules as H2S sensors and offers insight into their mechanistic pathways. Moreover, it collates the salient aspects of optical detection techniques and highlights the future scope for prospective exploration in this field based on the limitations of the existing H2S probes.

Separation and purification of fluorescent carbon dots - an unmet challenge.

Literature reports demonstrate versatile optical applications of fluorescent carbon dots (CDs) in biological imaging, full-color solid-state lighting, optoelectronics, sensing, anticounterfeiting and so on. The fluorescence associated with CDs may originate significantly from byproducts generated during their synthesis, which need to be eliminated to achieve error-free results. The significance of purification, specifically for luminescence-based characterizations, is highly critical and imperative. Thus, there is a pressing demand to implement consistent and adequate purification strategies to reduce sample complexity and thereby realize reliable results that can provide a tactical steppingstone towards the advancement of CDs as next-generation optical materials. The article focuses on the mechanism of origin of fluorescence from CDs and further demonstrates the different purification approaches including dialysis, centrifugation, filtration, solvent extraction, chromatography, and electrophoresis that have been adopted by various researchers. Furthermore, the fundamental separation mechanism, as well as the advantages and limitations of each of these purification techniques are discussed. The article finally provides the critical challenges of these purification techniques that need to be overcome to obtain homogeneous CD fractions that demonstrate coherent and reliable optical features for suitable applications.

Cellulose as an Eco-Friendly and Sustainable Material for Optical Anticounterfeiting Applications: An Up-to-Date Appraisal.

The falsification of documents, currency, pharmaceuticals, branded goods, clothing, food products, and packaging leads to severe consequences. Counterfeited products can not only pose health risks to consumers but also cause substantial economic losses that can negatively impact the global markets. Unfortunately, most anticounterfeiting strategies are easily duplicated due to rapid technological advancements. Therefore, innovative and cost-effective antiforgery techniques that can offer superior multilevel security features are continuously sought after. Due to the ever-growing global awareness of environmental pollution, renewable and eco-friendly native biopolymers are garnering wide attention in anticounterfeiting applications. This review highlights the potential use of cellulose-based eco-friendly materials to combat the counterfeiting of goods. The initial section of the review focuses on the structure, properties, and chemical modifications of cellulose as a sustainable biomaterial. Further, the topical developments reported on cellulose and nanocellulose-based materials used as fluorescent security inks, films, and papers for achieving protection against counterfeiting are presented. The studies suggest the convenient use of celluose and modified cellulose materials for promising optical antiforgery applications. Furthermore, the scope for future research developments is also discussed based on the current critical challenges in the fabrication of cellulose-based materials and their anticounterfeit applications.

Naphthalimide derivatives as fluorescent probes for imaging endogenous gasotransmitters.

Gasotransmitters have gained significant recognition attributed to their evident biological impacts, and is accepted as a promising and less-explored area with immense research scope. The three-member family comprising of nitric oxide, carbon monoxide and hydrogen sulphide as endogenous gaseous signaling molecules have been found to elicit a plethora of crucial biological functions, spawning a new research area. The sensing of these small molecules is vital to gain deeper insights into their functions, as they can act both as a friend or a foe in mammalian systems. The initial sections of the review present the physiological and pathophysiological roles of these endogenous gas transmitters and their synergistic interactions. Further, various detection approaches, especially the usage of fascinating features of 1,8-naphthalimide as fluorescent probe in the detection and monitoring of these small signaling molecules are highlighted. The current limitations and the future scope of improving the sensing of the three gasotransmitters are also discussed.

Experimental and molecular dynamics studies on aggregation behaviour of salicylaldehyde azine ester.

Aggregation phenomena arise predominantly due to self-organisation of molecules to form supramolecular assemblies leading to restriction of intramolecular motions. In the present study, the solvent-induced aggregation of salicylaldehyde azine ester (SAE) was comprehensively investigated through experimental techniques, and classical molecular dynamics simulations (MDS). The emission spectra and particle sizes of SAE in THF-water mixtures confirmed the formation of nanoaggregates. The interaction of SAE aggregates with the solvent mixture was studied using Fourier-transform Infrared spectroscopy. The optical microscopy images and surface morphology analysis reinforced the nanoaggregate formation of SAE in solvent mixtures with increasing water fractions. The average number of H-bonds, diffusion coefficients and trajectory density contours of the aggregates were investigated through MDS studies, which provided atomistic perceptions into the formation of rod-like SAE nanoaggregates. The combined results of experimental and theoretical studies offer deeper insights into the self-aligning tendency of SAE in THF-water mixtures.

A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells.

The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4-(6-nitro-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4-nitro-1,8-naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR-aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF-7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions.

Emerging trends in aggregation induced emissive luminogens as bacterial theranostics.

The emergence and spread of pathogenic bacteria, particularly antibiotic-resistant strains pose grave global concerns worldwide, which demand for the rapid development of highly selective and sensitive strategies for specific bacterial detection, identification, imaging and therapy. The fascinating feature of aggregation-induced emissive molecules (AIEgens) to display fluorescence in aggregate form can be suitably coupled with nanotechnology for developing theranostic AIE dots that can offer convenient and customised functions such as sensing, imaging, detection, discrimination and cell kill of different bacterial types. The initial section of the article reveals the necessity for incorporating diagnostic imaging with antibacterial therapy, while the latter part delivers mechanistic insights on the benefits of AIE fluorophores in theranostic applications. Further, the review illustrates the recent advancements of AIEgens as theranostic nanolights in bacterial detection, identification and eradication. The review is organised according to the different classes of AIE-active bacterial theranostics such as carrier-free nanoprodrugs, nanomachines for synergistic imaging-guided cancer treatment and bacterial kill, AIE polymers, bioconjugates and nanoparticle carriers. By elucidating their design principles and applications, as well as highlighting the recent trends and perspectives that can be further explored, we hope to instill more research interest in AIE bacterial theranostics for future translational research.HighlightsCombination of aggregation induced emissive fluorophores and nanotechnology for developing bacterial theranostics.AIE theranostics with customised functions for bacterial imaging, detection, discrimination and cell kill.

A mechanistic insight into benefits of aggregation induced emissive luminogens in cancer.

Exploration of advanced chemotheranostics that benefit from a combined in vivo strategy of cancer diagnosis and chemotherapy simultaneously is highly valued and will expose novel possibilities in modifying treatment and reduce side effects. In recent years, nanodrug delivery systems that incorporate aggregation-induced emissive luminogens (AIEgens) have been developed to track and monitor anticancer drug release, trace translocation processes and predict chemotherapeutic responses. There are several classes of AIEgen based chemotheranostics such us stimuli-responsive nanoprodrugs, pH-sensitive mesoporous silica nanocarriers, supramolecular polymer systems, drug encapsulated carriers, carrier-free nanodrugs, self-indicating drug delivery nanomachines and AIEgen-prodrug co-assembly. The present review conveys mechanistic insight into the benefits of AIEgens in the theranostic application by illustrating the recent breakthroughs in chemotheranostic nanomedicines that incorporate these unique fluorophores as signal reporters. The perspectives that can be further explored are also highlighted with the hope to instil more research interest in the advancement of AIE active cancer chemotheranostics for imaging and treatment in vivo.HIGHLIGHTSAggregation induced emissive materials (AIEgens) exhibit unique advantages over conventional luminogens for synergistic diagnosis and chemotherapy of cancer in vivo.The combination of AIE and nanotechnology offers an excellent platform to fabricate advanced chemotheranostics for cancer therapy.

Hypoxia-responsive nanoparticle based drug delivery systems in cancer therapy: An up-to-date review.

Hypoxia is a salient feature observed in most solid malignancies that holds a pivotal role in angiogenesis, metastasis and resistance to conventional cancer therapeutic approaches, and thus enables cancer progression. However, the typical characteristics of hypoxic cells such as low oxygen levels and highly bio-reductive environment can offer stimuli-responsive drug release to aid in tumor-specific chemo, radio, photodyanamic and sonodynamic therapies. This approach based on targeting the poorly oxygenated tumor habitats offers the prospective to overcome the difficulties that arises due to heterogenic nature of tumor and could be possibly used in the design of diagnostic as well as therapeutic nanocarriers for targeting various types of solid cancers. Consequently, hypoxia triggered nanoparticle based drug delivery systems is a rapidly progressing research area in developing effective strategies to combat drug-resistance in solid tumors. The present review presents the recent advances in the development of hypoxia-responsive nanovehicles for drug delivery to heterogeneous tumors. The initial sections of the article provides insights into the development of hypoxia in growing cancer and its role in disease progression. The current limitations and the future prospective of hypoxia-stimulated nanomachines for cancer treatment are also discussed.

Azodyes as markers for tumor hypoxia imaging and therapy: An up-to-date review.

Tumor hypoxia is the low tissue oxygen levels seen characteristically in rapidly proliferating and expanding neoplasms. It affects both malignant tumor cells and its microenvironment, resulting in dysfunctional neovascularization. This leads to epithelial-to-mesenchymal transition phenotype, facilitating tumor progression through cell mobility, invasion, and metastasis. The hypoxic condition in solid tumors is thus an indicator of the process of cancer progression towards an aggressive malignant phenotype with an enhanced possibility of metastasis and resistance to treatment. Advancements in the detection of tumor hypoxia and its utilization as a treatment modality in solid tumors are highly imperative. The use of fluorescent probes is an evolving field for detecting hypoxic tumors in biological systems. The present review is an attempt to provide a contextual knowledge on the prominent role of tumor hypoxia in cancer progression and dissemination. The use of azodyes in detecting tumor hypoxia aiding in cancer diagnosis through fluorescence off-on imaging and azodye-based hypoxia selective pro-drugs for assisting cancer therapy are presented. The limitations of fluorescence based hypoxia imaging and further investigations desired for clinical usage of azodye based hypoxic probes for fluorescence imaging are also considered.

Naphthalimides in fluorescent imaging of tumor hypoxia - An up-to-date review.

Hypoxia is a distinctive characteristic of advanced solid malignancies that results from a disparity between oxygen supply and its consumption. The degree of hypoxia is believed to have adverse prognostic significance. Therefore detecting cellular hypoxia can potentially offer insights into the grade of tumour as well as its evolution towards a progressive malignant phenotype, which clinically translates to greater metastatic potential and treatment resistance. Fluorescence imaging to visualize hypoxia in biological systems is a minimally-invasive method. Recently there are several reports on interdisciplinary research that aims at developing functional probes that can be efficiently used for non-invasive imaging of hypoxic tumours. Upregulated levels of nitroreductase (NTR) is detected in hypoxic solid malignancies, and this characteristic feature is increasingly utilized in the development of NTR-targeted fluorescent molecules to selectively sense hypoxia in vivo. The present review summarizes various reports published on the design concepts of nitro naphthalimide-based bio-reductive fluorescent sensors that can be applied noninvasively to image hypoxia in cancer.

Homology Modeling and Docking Studies of Bcl-2 and Bcl-xL with Small Molecule Inhibitors: Identification and Functional Studies.

Apoptosis is a vital physiological process, which is observed in various biological events. The anti-apoptotic and pro-apoptotic members of Bcl-2 family are the most characterized proteins which are involved in the regulation of apoptotic cell death. The anti-apoptotic proteins such as Bcl-2 and Bcl-xL prevent apoptosis, whereas pro-apoptotic members like Bax and Bak, elicit the release of caspases from death antagonists inducing apoptosis. Thus, the Bcl-2 family of proteins play a vital role in controlling programmed cell death. Over expression of anti-apoptotic Bcl-2 proteins are often directly associated with various kinds of cancer. Developing suitable inhibitors for controlling the elevated levels of these proteins got much attention in last decade. Structural biology techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography, homology modeling and molecular docking play a significant role in identifying the key inhibitors of these proteins. The authors have developed and tested successfully, several series of indole pharmacore containing inhibitors for Bcl-2 and Bcl-xL proteins based on the homology modeling, docking and suitable biochemical and apoptosis assays. This review provides a summary of potential inhibitor molecules developed for Bcl-2 and Bcl-xL proteins, as well as the the key residues of these proteins interacting with potential drug molecules. The present appraisal also focuses on the role of computational algorithms in developing potential drug molecules,with more emphasis on the role of homology modeling and docking studies in developing inhibitors for Bcl- 2, and Bcl-xL proteins in cancer therapy.

Bisindole-oxadiazole hybrids, T3P® -mediated synthesis, and appraisal of their apoptotic, antimetastatic, and computational Bcl-2 binding potential.

In the pursuit of novel anticancer leads, new bisindole-oxadiazoles were synthesized using propyl phosphonic anhydride as a mild and efficient reagent. The molecule, 3-[5-(1H-indol-3-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indole (3a) exhibited selective cytotoxicity to MCF-7 cells with a cell cycle arrest in the G1 phase. The mechanism of cytotoxicity of 3a involved caspase-2-dependent apoptotic pathway with characteristic apoptotic morphological alterations as observed in acridine orange/ethidium bromide and Hoechst staining. The wound healing migratory assay exhibited an intense impairment in the motility of MCF-7 cells on incubation with 3a. Docking simulations with anti-apoptotic protein Bcl-2, which is also involved in cancer metastasis displayed good affinity and high binding energy of 3a into the well characterized BH3 binding site. The positive correlation between the Bcl-2 binding studies and the results of in vitro investigations exemplifies compound 3a as a lead molecule exhibiting MCF-7 differential cytotoxicity via apoptotic mode of cell death in addition to its anti-metastatic activity.

Indole-coumarin-thiadiazole hybrids: An appraisal of their MCF-7 cell growth inhibition, apoptotic, antimetastatic and computational Bcl-2 binding potential.

Cancer therapeutic potential of thiadiazole hybrids incorporating pharmacologically active indole and coumarin moieties have not been explored much. In the current investigation, three new thiadiazole hybrids with spacers of varying lengths linking indole and thiadiazole units were synthesized and their structures were well-established using various spectroscopic techniques. 3-(1-(5-(3-(1H-indol-3-yl)propyl)-1,3,4-thiadiazol-2-ylimino)ethyl)-6-bromo-2H-chromen-2-one (IPTBC) exhibited dose-dependent cytotoxicity in breast adenocarcinoma (MCF-7) cells. The circumvention of apoptosis is a prominent hallmark of cancer and hence triggering apoptosis in specific cancer cells is one of the convenient and widely used approaches for the development of anticancer chemotherapeutics. The induction of apoptosis upon treatment with IPTBC was confirmed by multiple apoptosis assays like Acridine orange-ethidium bromide, Hoechst staining, TUNEL staining, and colorimetric quantification using APOPercentage™ Apoptosis assay. The apoptosis initialisation through the active involvement of caspases was confirmed by caspase profiling tests. The wound healing assay displayed an intense impairment in the motility of MCF-7 cells suggesting the anti-metastatic potential of IPTBC. The ability of IPTBC to inhibit the antiapoptotic Bcl-2 protein by acting as a small molecule BH3 mimetic was explored through docking simulation studies. Although auxiliary investigations are warranted with this promising thiadiazole hybrid IPTBC, the perspective anticancer potential through programmed cell death, anti-metastatic and probable Bcl-2 inhibitory action will enable its further exploration in oncology.

Nano-Chitosan Particles in Anticancer Drug Delivery: An Up-to-Date Review.

BACKGROUND: Cancer is one of the most awful lethal diseases all over the world and the success of its current chemotherapeutic treatment strategies is limited due to several associated drawbacks. The exploration of cancer cell physiology and its microenvironment has exposed the potential of various classes of nanocarriers to deliver anticancer chemotherapeutic agents at the tumor target site. These nanocarriers must evade the immune surveillance system and achieve target selectivity. Besides, they must gain access into the interior of cancerous cells, evade endosomal entrapment and discharge the drugs in a sustained manner. Chitosan, the second naturally abundant polysaccharide is a biocompatible, biodegradable and mucoadhesive cationic polymer which has been exploited extensively in the last few years in the effective delivery of anticancer chemotherapeutics to the target tumor cells. Therapeutic agent-loaded surface modified chitosan nanoparticles are established to be more stable, permeable and bioactive. CONCLUSION: This review will provide an up-to-date evidence-based background on recent pharmaceutical advancements in the transformation of chitosan nanoparticles for smart anticancer therapeutic drug delivery. HIGHLIGHTS: • Efforts to improve cancer chemotherapy by exploiting the intrinsic differences between normal and neoplastic cells to achieve maximum effective drug delivery to target cancer cells through bioengineered chitosan nano delivery vectors are discussed. • The easy manipulation of surface characteristics of chitosan based nanoparticles by various functionalization methods to achieve targeted drug delivery proves its potential to be an essential tool for the advancement of anticancer drug-delivery vectors.

Efficient T3P® mediated synthesis, differential cytotoxicity and apoptosis induction by indolo-triazolo-thiadiazoles in human breast adenocarcinoma cells.

The limited efficacy of marketed anticancer agents demands the design of novel target-specific hybrid molecules incorporating multiple bioactive pharmacores to combat cancer. In the present study, a one-pot simple and efficient T3P® mediated procedure for the preparation of twelve new 3-(substituted- [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazolo)-1H-indoles with short reaction times, easy workup procedure, good yields, and purity of products is described. Cytotoxicity assay (MTT), flow-cytometric univariate cell cycle analysis, Annexin V-FITC staining and DNA fragmentation for cell death mechanism suggested that compound 3d with chloro-substituted phenyl ring induced enhanced cytotoxicity by an apoptotic pathway with high differential toxicity to breast adenocarcinoma cells (MCF-7) when compared with normal human dermal fibroblast cells. Additionally, the interaction between the BH3 domain of anti-apoptotic proteins Bcl-2 and Bcl-xL with the pharmacophore 3d was examined by molecular docking simulations to assess its potential to induce apoptosis. The docking solutions were proposed to explain the observed selectivity of 3d to Bcl-xL protein. From the present findings, the lead compound, 3d exhibited better anticancer activity when related to the other synthesized molecules with specific action on MCF-7 cells and hence can be considered as a plausible candidate chemo-therapeutic agent, although this warrants further experimentation.

Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To-Date Evidence-Based Review.

Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm "one-compound-one-target" has failed and subsequently shifted to two-drug cocktail and recently the "multi-target approach" in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed.

Indole based Tubulin Polymerization Inhibitors: An Update on Recent Developments.

The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αß heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.

Indole based tubulin polymerization inhibitors: An update on recent developments.

The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αß heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.