Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry.

INTRODUCTION: Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder-related quality of life (QoL) and the reasons for CIC cessation. METHODS: The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder-related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder-related QoL. RESULTS: There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI-QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI-QoL difficulties). CONCLUSIONS: Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.

Patient Reported Bladder Related Symptoms and Quality of Life after Spinal Cord Injury with Different Bladder Management Strategies.

PURPOSE: Neurogenic bladder significantly impacts individuals after spinal cord injury. We hypothesized that there would be differences in bladder related symptoms and quality of life for 4 common bladder management methods. MATERIALS AND METHODS: In this prospective observational study we measured neurogenic bladder related quality of life after spinal cord injury. Study eligibility included age 18 years or greater and acquired spinal cord injury. Bladder management was grouped as 1) clean intermittent catheterization, 2) an indwelling catheter, 3) surgery (bladder augmentation, a catheterizable channel or urinary diversion) and 4) voiding (a condom catheter, involuntary leaking or volitional voiding). The primary outcomes were the NBSS (Neurogenic Bladder Symptom Score) and the SCI-QoL Difficulties (Spinal Cord Injury Quality of Life Measurement System Bladder Management Difficulties). Secondary outcomes were the NBSS subdomains and satisfaction with urinary function. Multivariable regression was done to establish differences between the groups, separated by level. RESULTS: Of the 1,479 participants enrolled in the study 843 (57%) had paraplegia and 894 (60%) were men. Median age was 44.9 years (IQR 34.4-54.1) and median time from injury was 11 years (IQR 5.1-22.4). Bladder management was clean intermittent catheterization in 754 cases (51%), an indwelling catheter in 271 (18%), surgery in 195 (13%) and voiding in 259 (18%). In regard to primary outcomes, in cases of paraplegia and tetraplegia an indwelling catheter and surgery were associated with fewer urinary symptoms on the NBSS compared to clean intermittent catheterization while voiding was associated with more symptoms. In paraplegia and tetraplegia cases surgery was associated with fewer bladder management difficulties according to the SCI-QoL Difficulties. In regard to secondary outcomes, surgery was associated with improved satisfaction in individuals with paraplegia or tetraplegia. CONCLUSIONS: In individuals with spinal cord injury fewer bladder symptoms were associated with an indwelling catheter and surgery, and worse bladder symptoms were noted in voiding individuals compared to those on clean intermittent catheterization. Satisfaction with the urinary system was improved after surgery compared to clean intermittent catheterization.

The effects of augmentation cystoplasty and botulinum toxin injection on patient-reported bladder function and quality of life among individuals with spinal cord injury performing clean intermittent catheterization.

AIMS: Clean intermittent catheterization (CIC) is recommended after spinal cord injury (SCI) because it has the least complications, however, CIC has a high discontinuation rate. We hypothesized that bladder botulinum toxin injection or augmentation cystoplasty may improve satisfaction with CIC. METHODS: The NBRG registry is a multicenter, prospective, observational study asking SCI participants about neurogenic bladder (NGB) related quality of life (QoL). In this study, participants performing CIC as primary bladder management were categorized into 3 groups: (1) CIC alone (CIC); (2) CIC with botulinum toxin (CIC-BTX); and (3) CIC with augmentation cystoplasty (CIC-AUG). Outcomes included primary: Neurogenic Bladder Symptom Score (NBSS) and SCI-QoL Bladder Management Difficulties, and secondary: NBSS subdomains (Incontinence, Storage & Voiding, Consequences) and the NBSS final question (satisfaction with urinary function). Multivariable regression, controlling for multiple factors was used to establish differences between the three groups. RESULTS: Eight hundred seventy-nine participants performed CIC as primary bladder management and had the following characteristics: mean age 43.4 (±12.9) and years from injury 13.7 (±10.7), tetraplegia in 284 (32%), and 543 (62%) were men. Bladder management was CIC in 593 (67%), CIC-BTX in 161 (19%), and CIC-AUG in 125(15%). Primary outcomes: CIC-AUG had associated improved total NBSS versus CIC(-3.2(-5.2 to -1.2), P = 0.001 and CIC-BTX(-3.9(-6.3 to -1.6), P = 0.001), CIC-AUG also had better SCI-QoL Difficulties scores versus CIC(-4(-5.48 to -2.53, P < 0.001) and CIC-BTX(-4.4(-6.15 to -2.65, P < 0.001). SECONDARY OUTCOMES: CIC-AUG had associated improved Incontinence and Satisfaction scores versus CIC and CIC-BTX. CONCLUSIONS: Compared to patients performing CIC with or without botulinum toxin treatment, those with augmentation cystoplasty had associated better urinary function and satisfaction with their urinary symptoms.

Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides.

The synthesis of novel pyrazolylnucleosides 3a-e, 4a-e, 5a-e, and 6a-e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a-e and 6a-e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI50 9.3 µM) and breast cancer cell line HS 578T (GI50 3.0 µM).

Kinase-targeted cancer therapies: progress, challenges and future directions.

The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are associated with human cancer initiation and progression. The recent development of small-molecule kinase inhibitors for the treatment of diverse types of cancer has proven successful in clinical therapy. Significantly, protein kinases are the second most targeted group of drug targets, after the G-protein-coupled receptors. Since the development of the first protein kinase inhibitor, in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment of malignancies such as breast and lung cancer. Furthermore, about 150 kinase-targeted drugs are in clinical phase trials, and many kinase-specific inhibitors are in the preclinical stage of drug development. Nevertheless, many factors confound the clinical efficacy of these molecules. Specific tumor genetics, tumor microenvironment, drug resistance, and pharmacogenomics determine how useful a compound will be in the treatment of a given cancer. This review provides an overview of kinase-targeted drug discovery and development in relation to oncology and highlights the challenges and future potential for kinase-targeted cancer therapies.

Convenient access to 5-arylisoindolo[2,1- α]quinolin-11(6a H)-ones.

Substituted isoindoloquinolinones were obtained from N-aryl-3-hydroxyisoindolinones and aryl alkynes under Lewis acid-catalyzed conditions in 30-99% yields.

Study protocol: patient reported outcomes for bladder management strategies in spinal cord injury.

BACKGROUND: The majority of spinal cord injury (SCI) patients have urinary issues, such as incontinence, retention, and frequency. These problems place a significant burden on patients' physical health and quality of life (QoL). There are a wide variety of bladder management strategies available to patients with no clear guidelines on appropriate selection. Inappropriate bladder management can cause hospitalizations and serious complications, such as urosepsis and renal failure. Patients believe that both independence and ability to carry out daily activities are just as important as physical health in selecting the right bladder-management strategy but little is known about patient's QoL with different bladder managements. Our study's aim is to assess patient reported QoL measures with various bladder managements after SCI. This manuscript describes the approach, study design and common data elements for our central study. METHODS: This is a multi-institutional prospective cohort study comparing three different bladder-management strategies (clean intermittent catheterization, indwelling catheters, and surgery). Information collected from participants includes demographics, past medical and surgical history, injury characteristics, current and past bladder management, and SCI /bladder-related complications. Patient reported outcomes and QoL questionnaires were administered at enrollment and every 3 months for 1 year. Aims of this study protocol are: (1) to assess baseline QoL differences between the three different bladder-management strategies; (2) determine QoL impact when those using either form of catheter management undergo a surgery over the 1 year of follow-up among patients eligible for surgery; (3) assess the effects of changes in bladder management and complications on QoL over a 1-year longitudinal follow-up. DISCUSSION: By providing information about patient-reported outcomes associated with different bladder management strategies after SCI, and the impact of bladder management changes and complications on QoL, this study will provide essential information for shared decision-making and guide future investigation. TRIAL REGISTRATION: Trial registration number: www.clinicaltrials.gov : Identifier: NCT0261608; U.S. National Library of Medicine, wwwcf.nlm.nih.gov : Identifier: HSRP20153564.

Investigation of fatty acid conjugates of 3,5-bisarylmethylene-4-piperidone derivatives as antitumor agents and human topoisomerase-IIα inhibitors.

A series of five 3,5-bisarylidene-4-piperidones designed as analogs of curcumin and their twenty five fatty acid conjugates were synthesized as candidate anticancer agents. The fatty acid conjugates were designed for efficient delivery of these compounds at the targeted cancer sites. The cytostatic potential of these compounds was evaluated against three representative cancer cell lines namely murine leukemic L1210 cells, and human T-lymphocyte CEM cells and cervical HeLa cells. Most compounds were found to exhibit significant anti-cancer activity in vitro. QSAR studies indicated electrophilicity of these compounds towards cellular nucleophiles may have a key role to play in their cytostatic activity. Representative compounds were also tested for topoisomerase IIα inhibitory potential, which indicated strong catalytic inhibition of the enzyme in vitro. The data showed that the fatty acid conjugates also possessed robust antioxidant activity in multiple analyses. This study also indicated that these compounds prompted significantly lower cellular damage in human fibroblasts than a currently used cancer drug sorafenib in vitro. The wide spectrum of anticancer action, supplemented with antioxidant potential along with non-toxic manifestations, certainly augment the anticancer candidacy of the novel fatty acid conjugates.

Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors.

Three series of novel 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones, designed as simplified analogs of curcumin with maleic diamide tether, were synthesized and bioevaluated. These compounds displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemic cells. In contrast, the related N-arylmaleamic acids possessed little or no cytotoxicity in these three screens. Design of these compounds was based on molecular modeling studies performed on a related series of molecule in a previous study. Representative title compounds were found to be significantly potent in inhibiting the activity of topoisomerase II alpha indicating the possible mode of action of these compounds. These compounds were also potent antioxidants in vitro and attenuated the AAPH triggered peroxyl radical production in human fibroblasts. Various members of these series were also well tolerated in both in vitro and in vivo toxicity analysis.

Aza-Diels-Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome.

The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels-Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.

Transition metal-free one-pot cascade synthesis of 7-oxa-2-azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones from biomass-derived levulinic acid under mild conditions.

An efficient, environmentally benign, transition-metal free, tandem C-N, C-O bond formation reaction is developed for the synthesis of tricyclic 7-oxa-2-azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones and their homologs from easily available starting materials, including renewable levulinic acid, a keto acid. The reaction of keto acids with methyl chloroformate and variously substituted o-aminobenzyl alcohols using triethylamine as a base in toluene at room temperature gave good to excellent yields. This newly developed protocol was successfully utilized for the synthesis of a variety of polycyclic 7-oxa-2-azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones and related compounds.

An efficient and expeditious synthesis of novel 2,2-dialkyl-2,3-dihydrobenzofurans from phenols and 2,2-dialkylacetaldehydes.

Reactions of 2,2-dialkylaldehydes with electronrich 2-naphthols and para-substituted phenols in presence of catalytic amount of p-TSA under closed vessel solvent-free microwave irradiation conditions resulted in formation of corresponding 2,2-dialkyl-1,2-dihydronaphtho[2,1-b]furans and 2,2-dialkyl-2,3-dihydrobenzofurans, respectively, in good to excellent yields. The effect of stoichiometry, temperature, and catalyst in reaction progress was systematically investigated. 14-Alkyl-14H-dibenzo[a, j]xanthenes was obtained as minor productswhen 2-naphthol and 6-bromo-2-naphthols were used as starting phenols. Simple phenols gave a lower yield of the 2,2-dialkyl-2,3-dihydrobenzofurans products than their electron-rich naphthalene counterparts. Also, xanthene-type products were not detected in case of simple phenols by GC­MS or column chromatography.

Acute rehospitalizations during inpatient rehabilitation for spinal cord injury.

OBJECTIVES: To investigate frequency of and reasons for readmission to acute care (RTAC) during inpatient rehabilitation after traumatic spinal cord injury (SCI), and to identify factors associated with RTAC. DESIGN: Prospective observational cohort. SETTING: Inpatient rehabilitation. PARTICIPANTS: Individuals with SCI (N=1376) consecutively admitted for inpatient rehabilitation; 1032 randomly selected for model development; 344 selected for model cross-validation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: RTAC, RTAC reasons, rehabilitation length of stay (LOS), discharge location and FIM, rehospitalization between discharge and year 1, and 1-year outcomes: FIM, Craig Handicap Assessment and Reporting Technique, and Patient Health Questionnaire-9. RESULTS: Participants (n=116; 11%) experienced RTAC with a total 143 episodes--96 patients experienced only 1 RTAC, while 14 had 2 RTACs, 5 had 3 RTACs, and 1 had 4 RTACs. The most common RTAC reasons were surgery (36%), infection (22%), noninfectious respiratory (14%), and gastrointestinal (8%). Mean days ± SD from rehabilitation admission to first RTAC was 27 ± 30 days. Seventy-four (7%) patients had at least 1 RTAC for medical reasons and 46 (4%) for surgical reasons. Regression analyses indicated several variables were associated with RTACs: greater admission medical severity, lower admission cognitive FIM, pressure ulcer acquired in acute care, and study site. Medical RTACs were associated with higher body mass index, lower admission cognitive and motor FIM, payer, and study site. Predictors of surgical RTAC were longer time from injury to rehabilitation admission and study site. After controlling for the other variables, the only outcome RTAC influenced was longer rehabilitation LOS. CONCLUSIONS: Approximately 11% of SCI patients experience RTAC during the course of rehabilitation for a variety of medical and surgical reasons. RTACs are associated with longer rehabilitation LOS.

Curcumin and its carbocyclic analogs: structure-activity in relation to antioxidant and selected biological properties.

Curcumin is the major phenolic compound present in turmeric (Curcuma longa L.). Curcumin and 15 novel analogs were investigated for their antioxidant and selected biological activities. Strong relationships between the structure and evaluated activity revealed that the compounds with specific functional groups and carbon skeleton had specific biological profiles. Among the compounds tested, the derivatives (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e), and (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)-cyclopentanone (3d) and the parent compound curcumin exhibited the strongest free radical scavenging and antioxidant capacity. Concerning the other biological activities studied the compound (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxy-phenyl)-acryloyl)cyclopentanone (3d) was the most potent angiotensin converting enzyme (ACE) inhibitor, while the derivatives (E)-2-(4-hydroxybenzylidene)-6-((E)-3-(4-hydroxyphenyl)acryloyl)cyclohexanone (2b), (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclohexanone (2e) and (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e) exhibited strong tyrosinase inhibition. Moreover, (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)-acryloyl)cyclohexanone (2e) was also found to be the strongest human HIV-1 protease inhibitor in vitro among the tested compounds. Cytotoxicity studies using normal human lung cells revealed that the novel curcumin as well as its carbocyclic analogs are not toxic.

Conducting polymer-based scaffolds for neuronal tissue engineering.

Neuronal tissue engineering has immense potential for treating neurological disorders and facilitating nerve regeneration. Conducting polymers (CPs) have emerged as a promising class of materials owing to their unique electrical conductivity and biocompatibility. CPs, such as poly(3,4-ethylenedioxythiophene) (PEDOT), poly(3-hexylthiophene) (P3HT), polypyrrole (PPy), and polyaniline (PANi), have been extensively explored for their ability to provide electrical cues to neural cells. These polymers are widely used in various forms, including porous scaffolds, hydrogels, and nanofibers, and offer an ideal platform for promoting cell adhesion, differentiation, and axonal outgrowth. CP-based scaffolds can also serve as drug delivery systems, enabling localized and controlled release of neurotrophic factors and therapeutic agents to enhance neural regeneration and repair. CP-based scaffolds have demonstrated improved neural regeneration, both in vitro and in vivo, for treating spinal cord and peripheral nerve injuries. In this review, we discuss synthesis and scaffold processing methods for CPs and their applications in neuronal tissue regeneration. We focused on a detailed literature review of the central and peripheral nervous systems.

The impact of sacral sensory sparing in motor complete spinal cord injury.

OBJECTIVE: To determine the effect of sensory sparing in motor complete persons with spinal cord injury (SCI) on completion of rehabilitation on neurologic, functional, and social outcomes reported at 1 year. DESIGN: Secondary analysis of longitudinal data collected by using prospective survey-based methods. SETTING: Data submitted to the National SCI Statistical Center Database. PARTICIPANTS: Of persons (N=4106) enrolled in the model system with a motor complete injury (American Spinal Injury Association Impairment Scale [AIS] grade A or B) at the time of discharge between 1997 and 2007, a total of 2331 (56.8%) completed a 1-year follow-up interview (Form II) and 1284 (31.3%) had complete data for neurologic (eg, AIS grade, injury level) variables at 1 year. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: AIS grade (A vs B) at 1 year, bladder management, hospitalizations, perceived health status, motor FIM items, Satisfaction With Life Scale, depressive symptoms, and social participation. RESULTS: Compared with persons with AIS grade A at discharge, persons with AIS grade B were less likely to require indwelling catheterization and be hospitalized and more likely to perceive better health, report greater functional independence (ie, self-care, sphincter control, mobility, locomotion), and report social participation in the first year postinjury. A greater portion of individuals with AIS grade B at discharge had improved neurologic recovery at 1 year postinjury than those with AIS grade A. Significant AIS group differences in 1-year outcomes related to physical health were maintained after excluding persons who improved to motor incomplete status for only bladder management and change in perceived health status. This recognition of differences between persons with motor complete injuries (AIS grade A vs B) has important ramifications for the field of SCI rehabilitation and research.

Derivatives of aryl amines containing the cytotoxic 1,4-dioxo-2-butenyl pharmacophore.

Several series of compounds containing the 1,4-dioxo-2-butenyl moiety have been prepared as candidate cytotoxins, including the methyl N-arylmaleamates, methyl N-arylfumaramates, and N-arylmaleimides. In addition, the N-arylisomaleimides were synthesized which are the structural isomers of N-arylmaleimides. These compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. Methyl N-arylfumaramates showed the highest cytotoxic potencies and, in particular, methyl N-(3,4-dichlorophenyl)fumaramate is six times more potent than melphalan towards L1210 cells and is equipotent with this drug in the Molt 4/C8 assay. Electrophilicity of compounds under investigation was demonstrated by carrying out thiolation using model benzyl mercaptan on representative compounds. Methyl N-(3,4-dichlorophenyl)fumaramate and methyl N-(4-chlorophenyl)maleamate inhibited human N-myristoyltransferase, a possible molecular target, in high micromolar range. QSAR and molecular modeling revealed some correlations between different structural features of a number of the molecules and cytotoxic potencies. Methyl N-arylfumaramates were well tolerated in mice in comparison to the analogs in other series of compounds tested. The data obtained in this investigation affords guidelines for preparing new series of molecules with greater potencies.

Novel and convenient synthesis of 1-(pyridinylmethyl)-2-naphthols and 1-(pyridinylmethylene)-2-tetralones from 2-tetralones.

The reaction of 2/4-pyridine carboxaldehyes with 2-tetralone analogs in the presence of catalytic amounts of Pd/C and trimethylsilyl chloride in DMF resulted in the formation of 1-(pyridin-2/4-ylmethyl)-2-naphthols in moderate to good yields as opposed to the expected 1-(pyridin-2/4-ylmethylene)-2-tetralones. 3-Pyridine carboxaldehyde, however, formed 1-(pyridin-3-ylmethylene)-2-tetralones with 2-tetralone analogs under similar conditions. When representative reactions were repeated in the presence of anhydrous HCl gas in acetic acid, including one with 3-pyridine carboxaldehyde, 1-(pyridinylmethyl)-2-naphthols were the only products obtained with significantly improved yields. A possible mechanism explaining these results is discussed.

_ 2009 review and revisions of the international standards for the neurological classification of spinal cord injury.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents.

A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase IIalpha via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIalpha and displayed cytostatic activity in the nanomolar range.