PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia.

OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management. METHODS: Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset. RESULTS: Three streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms. CONCLUSIONS: Our streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended.

High HIV prevalence in gestational trophoblastic neoplasia patients.

OBJECTIVE: To assess the HIV prevalence in patients diagnosed with gestational trophoblastic neoplasia (GTN). DESIGN: A retrospective single centre cohort study. METHODS: A database from the Sheffield Trophoblastic Disease Centre (STDC), Sheffield, UK was searched between 1st January 2015 and 31st December 2021. A total of 3,591 patients were referred to STDC with a diagnosis of gestational trophoblastic disease (GTD), of which 221 (6.2%) were treated for GTN. The prevalence of HIV-positive tests in GTN patients was assessed. RESULTS: HIV testing was performed in 93% GTN patients ( n  = 205/221). Overall, 1.3% of GTN patients ( n  = 3/221) were HIV-positive, involving two known HIV-positive patients and one new diagnosis. This equates to a HIV prevalence of 14 : 1000, which is ∼7 to 9× higher than the HIV prevalence in Sheffield (1.9 per 1000) and Yorkshire and Humber (1.5 per 1000). CONCLUSION: Given the extremely high HIV prevalence in our population, 'opt out' HIV testing is recommended within our specialist trophoblastic centre for all referred GTD and GTN patients. There is little reason to suspect that the prevalence of HIV-positive patients is any lower in the cohort of GTD patients referred to specialist trophoblastic centres for hCG screening alone, without requiring chemotherapy, particularly considering that most GTN arises from GTD.

Size economy and first hyperpolarizability: synthesis and nonlinear optical behavior of ferrocene-based donor-acceptor chromophores lacking π-linkers.

The question of size economy in the design of chromophores for nonlinear optics is addressed in this investigation. We have synthesized directly linked donor-acceptor dyads, which lack a π-conjugated linker, the presence of which is usually considered obligatory in materials designed for nonlinear optics. Correlating linear optical data, electrochemical data, computational data and hyper Rayleigh scattering (HRS) data on ferrocene (Fc) based dyads, we demonstrate that the first hyperpolarizability of such size economical chromophores is significantly better compared to that of Fc based, traditional, larger, donor-π-acceptor chromophores. Arguably, a larger π-conjugated linker decreases the electronic communication between the donor and the acceptor and weakens the intramolecular charge transfer in such chromophores.

Bis-cyanostilbene based fluorescent materials: A rational design of AIE active probe for hypochlorite sensing.

In the present investigation cyanostilbene based molecular probes, PCS and PCO, bearing N,N-dimethylthiocarbamate and N,N-dimethylcarbamoyal groups, respectively, have been synthesised. These probes exhibit AIEE activity in their aggregated state in the mixed solvent system of THF: H2O by way of turning on their emission, which has also been observed in powder, neat thin films and hybrid polymer films. While the probe PCO is silent to ClO-, PCS exhibits a significant response towards ClO- rationalised on the basis of HOCl specific oxidation of thiocarbamate, which is also extended to detect ClO- in water samples. Additionally, applicability of the test strips of PCS for rapid on-site detection of ClO- has been demonstrated. The experimental results are supplemented by the theoretical calculations wherever possible.

Positive and Neutral Needleless Connectors: A Comparative Study of Central-line Associated Bloodstream Infection, Occlusion, and Bacterial Contamination of the Connector Lumen.

A pragmatic, multiphase prospective quality improvement initiative was performed to determine whether a positive displacement connector (PD) causes reduction of central line-associated bloodstream infection (CLABSI), occlusion, and catheter hub colonization when compared with a neutral displacement connector with alcohol disinfecting cap (AC). Patients with an active central vascular access device (CVAD) were enrolled March 2018 to February 2019 (P2) and compared to the prior year (P1). Two hospitals were randomized to use PD without AC (Hospital A) and with AC (Hospital B). Two hospitals utilized a neutral displacement connector with AC (Hospitals C and D). CVADs were monitored for CLABSI, occlusion, and bacterial contamination during P2. Of the 2454 lines in the study, 1049 were cultured. CLABSI decreased in all groups between P1 and P2: Hospital A, 13 (1.1%) to 2 (0.2%); Hospital B, 2 (0.3%) to 0; and Hospitals C and D, 5 (0.5%) to 1 (0.1%). CLABSI reduction was equivalent between P1 and P2 with and without AC, at around 86%. The rate of occlusion per lumen was 14.4%, 12.1%, and 8.5% for Hospitals A, B and C, D, respectively. Hospitals using PD had a higher rate of occlusion than those that did not (P = .003). Lumen contamination with pathogens was 1.5% for Hospitals A and B and 2.1% for Hospitals C and D (P = .38). The rate of CLABSI was reduced with both connectors, and PD reduced infections with and without the use of AC. Both connector types had low-level catheter hub colonization with significant bacteria. The lowest rates of occlusion were found in the group using neutral displacement connectors.

Julolidine-hydrazone based chemosensor for detection of Zn2+: Fluorescent in-situ formed Zn2+ complex discriminates PPi from ADP and ATP.

In the present investigation, we have designed and synthesised Zn2+ sensitive Julolidine-hydrazone (JSB) based chemosensor, which crystallised in a monoclinic crystal system with P21/c space group. The bare JSB was nonemissive, but in the presence of Zn2+ ions in solution it showed emission, ascribed to the chelation enhanced emission process, which is also utilised to detect Zn2+ in water samples. Comparing the chromaticity coordinates deduced from the emission colors of the JSB-Zn2+ in solution, powder and hybrid polymer thin film, using CIE (Commission Internationale de I'Eclairage 1931) chromaticity diagram, it was found that compared to the emission of the solution, the emission of the powder was red shifted, while that of the thin film was blue shifted. Further, the sensing of Zn2+ showed reversibility in the presence of pyrophosphate (PPi), which allowed quantification of PPi. Interestingly, in addition to the detection of PPi using the in-situ formed JSB-Zn2+ complex, the process was selective and discriminated PPi from ADP and ATP. The detection of PPi was rationalized via a decomplexation reaction, and translated in the construction of INHIBIT logic gate. Additionally, the possible use of the JSB coated sensor paper for the on-site detection of Zn2+ and subsequent JSB-Zn2+ complex for PPi ions has been demonstrated. The experimental results showed good correlation with the theoretical calculations wherever possible.

Towards hospital-on-chip supported by 2D MXenes-based 5th generation intelligent biosensors.

Existing public health emergencies due to fatal/infectious diseases such as coronavirus disease (COVID-19) and monkeypox have raised the paradigm of 5th generation portable intelligent and multifunctional biosensors embedded on a single chip. The state-of-the-art 5th generation biosensors are concerned with integrating advanced functional materials with controllable physicochemical attributes and optimal machine processability. In this direction, 2D metal carbides and nitrides (MXenes), owing to their enhanced effective surface area, tunable physicochemical properties, and rich surface functionalities, have shown promising performances in biosensing flatlands. Moreover, their hybridization with diversified nanomaterials caters to their associated challenges for the commercialization of stability due to restacking and oxidation. MXenes and its hybrid biosensors have demonstrated intelligent and lab-on-chip prospects for determining diverse biomarkers/pathogens related to fatal and infectious diseases. Recently, on-site detection has been clubbed with solution-on-chip MXenes by interfacing biosensors with modern-age technologies, including 5G communication, internet-of-medical-things (IoMT), artificial intelligence (AI), and data clouding to progress toward hospital-on-chip (HOC) modules. This review comprehensively summarizes the state-of-the-art MXene fabrication, advancements in physicochemical properties to architect biosensors, and the progress of MXene-based lab-on-chip biosensors toward HOC solutions. Besides, it discusses sustainable aspects, practical challenges and alternative solutions associated with these modules to develop personalized and remote healthcare solutions for every individual in the world.

Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia.

BACKGROUND: Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse. METHODS: Between January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5-6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR. RESULTS: In LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5-6 patients. The incidence of MTX toxicity was not influenced by BSA or weight. CONCLUSIONS: In the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.

Julolidine based red emitting ESIPT/AIE active material showing luminescence beyond excimer emission: An "on-off" emission response to Cu2.

A new julolidine-fluorene based excited state intramolecular proton transfer (ESIPT)/aggregate induced emission (AIE) active Schiff-base (JDF) has been synthesized and evaluated for its photophysical properties in solution and aggregated/solid states. The correlation between the emission behavior and the solid state crystal packing structure revealed the interplay of ESIPT coupled excimer reaction occurring in the solid state, which is one of the rare examples reported so far. For a comprehensive comparison, we synthesized a non-ESIPT methyl derivative (JDF-Me) of JDF capable of showing excimer emission only in the solid state. Further, JDF exhibits normal as well as keto emission in solution, upon addition of water, its poor solvent, that promotes aggregation, the fluorescence emission shows the preponderance of the excimer band in the low energy region. It was also interesting to note that in the solid state (thin films), JDF shows emission beyond the excimer emission, which is wavelength dependent. This is attributed to the formation of diverse clusters leading to the extended delocalization beyond excimers, and represents a clustering-triggered emission ascribing bright red color to the solid JDF. Such mélange of emission characteristics of JDF are responsible for the multicolor emission covering a broad range of electromagnetic spectrum, which is demonstrated by the confocal microscopy images of the JDF recorded in different states. Further, in its aggregated state, JDF recognized Cu2+ ions, selectively, manifested in the form of emission quenching via the interaction of Cu2+ ions with the oxygen and nitrogen atoms of JDF inhibiting the excimer formation.

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.

Analyte Detection: A Decade of Progress in the Development of Optical/Fluorescent Sensing Probes.

The development of selective and sensitive chemical sensors capable of detecting metal ions, anions, neutral species, explosives and hazardous substances, selectively and sensitively has attracted considerable interest of various research groups. The presence of such analytes within the permissible limits is often beneficial, but the excess amounts may lead to lethal effects to both the environment as well as the living organisms. Owing to the toxicity of the heavy metal ions, toxic anions and nitro-aromatics which are main constituents of explosives, the timely detection of these materials is most desirable to ensure safety and security of the mankind. In this personal account, we present several classes of molecular sensors that were specifically designed in our lab during the past decade for detecting several species in solutions, solid state as well as biological media. Modulation of the optical properties in response to the presence of guest species, led to selective and sensitive detection protocols, and was supported by the theoretical studies wherever possible. We have also extended the application of some of these probes for the on-site detection of analytes by developing the paper strips, glass slides and even the wool and cotton fabrics loaded with probes. One such development represents detection of palladium in human urine and blood samples collected from clinical samples. Additionally, the sensing events in some cases have successfully been reproduced in the live cancer cells. Based on the ease and cost-effective synthesis of the molecular probes, we hope that this account shall provide significant information to researchers in understanding the structure dependent sensing capabilities of the molecular probes.

Pore-scale visualization of hydrogen storage in a sandstone at subsurface pressure and temperature conditions: Trapping, dissolution and wettability.

HYPOTHESIS: Underground hydrogen (H2) storage is a potentially viable solution for large-scale cyclic H2 storage; however, the behavior of H2 at subsurface pressure and temperature conditions is poorly known. This work investigates if the pore-scale displacement processes in H2-brine systems in a porous sandstone can be sufficiently well defined to enable effective and economic storage operations. In particular, this study investigates trapping, dissolution, and wettability of H2-brine systems at the pore-scale, at conditions that are realistic for subsurface H2 storage. EXPERIMENTS: We have performed in situ X-ray imaging during a flow experiment to investigate pore-scale processes during H2 injection and displacement in a brine saturated Bentheimer sandstone sample at temperature and pressure conditions representative of underground reservoirs. Two injection schemes were followed for imbibition: displacement of H2 with H2-equilibrated brine and with non-H2-equilibrated brine. The results from the two cycles were compared with each other. FINDINGS: The sandstone was found to be wetting to the brine and non-wetting to H2 after both displacement cycles, with average contact angles of 54° and 53° for H2-equilibrated and non-H2-equilibrated brine respectively. We also found a higher recovery of H2 (43.1%) when displaced with non-H2-equilibrated brine compared to that of H2-equilibrated brine (31.6%), indicating potential dissolution of H2 in the unequilibrated imbibing brine at reservoir conditions. Our results suggest that underground H2 storage may indeed be a suitable strategy for energy storage, but considerable further research is needed to fully comprehend the pore-scale interactions at reservoir conditions.

Synthesis and Nonlinear Optical Behavior of Thermally Stable Chromophores Based on 9,9-Dimethyl-9H-fluoren-2-amine: Improving Intrinsic Hyperpolarizability through Modulation of "Push-Pull".

Improvement in the first hyperpolarizability (ßHRS) as well as intrinsic hyperpolarizability (ßint) of chromophores based on 9,9-dimethyl-9H-fluoren-2-amine through modulation of the conjugation pathway is described. A series of six novel chromophores with "linear" conjugation showed significant enhancement of ßHRS as well as ßint compared to the counterparts lacking a "linear" conjugation but having an identical combination of donor, acceptor, and the intervening π-conjugated linker. The hyperpolarizability (ßHRS as well as ßint) values of the new series measured using hyper-Rayleigh scattering exceeded the apparent limit set by the latter set of fluorene-based chromophores. The experimental results are analyzed and interpreted in the context of linear optical properties, single-crystal X-ray analysis, electrochemistry, etc. and corroborated by theoretical studies. We find that modulation of the "push-pull" of the conjugation pathway in these donor-acceptor chromophores compares favourably with the corresponding changes in the optical gaps, transition dipole moments, and dipole moment difference between the ground and excited states.

Fluorene-Chloroquine Hybrids: Synthesis, in†vitro Antiplasmodial Activity, and Inhibition of Heme Detoxification Machinery of Plasmodium falciparum.

Fluorene-chloroquine hybrids have been identified as a new promising class of antiplasmodial agents. The most active compound 9 d exhibited good in vitro antiplasmodial activity against a chloroquine-sensitive NF54 strain of the human malaria parasite Plasmodium falciparum with an IC50 value of 139 nM. UV-visible absorption, FTIR spectral and 1 H NMR titration data corroborated the binding of 9 d to monomeric and µ-oxodimeric heme as well as inhibition of ß-hematin formation, which collectively supported the inhibition of heme detoxification machinery in P. falciparum. In silico docking studies revealed the binding interactions of the hybrids in the active site of the wild type as well as quadruple mutant of Pf-DHFR-TS dihydrofolate enzyme. Further, the ADMET parameters were predicted and were in good agreement with the expected values, suggesting the drug likeness of the synthesized hybrid molecules.

Evaluation of the Dynamic Interfacial Tension between Viscoelastic Surfactant Solutions and Oil Using Porous Micromodels.

Interfacial tension (IFT) is a crucial parameter in many natural and industrial processes, such as enhanced oil recovery and subsurface energy storage. IFT determines how easy the fluids can pass through pore throats and hence will decide how much residual fluids will be left behind. Here, we use a porous glass micromodel to investigate the dynamic IFT between oil and Armovis viscoelastic surfactant (VES) solution based on the concept of drop deformation while passing through a pore throat. Three different concentrations of VES, that is, 0.5, 0.75, and 1.25% vol% prepared using 57 K ppm synthetic seawater, were used in this study. The rheology obtained using a rheometer at ambient temperature showed zero shear viscosity of 325, 1101, and 1953 cP for 0.5%, 0.75%, and 1.25% VES, respectively, with a power-law region between 2 and 50 1/s. The dynamic IFT increases with the shear rate and then reaches a plateau. The results of IFT were compared with those obtained from the spinning drop method, which shows 97% accuracy for 1.25% VES, whereas the accuracy decreased to 65% for 0.75 VES and 51% for 0.5% VES. The findings indicate that we can reliably estimate the IFT of VES at higher concentrations directly during multiphase flow in porous micromodels without the need to perform separate experiments and wait for a long time to reach equilibrium.

Thiazolothiazole based donor-π-acceptor fluorophore: Protonation/deprotonation triggered molecular switch, sensing and bio-imaging applications.

Stimuli modulated photophysical properties of a new asymmetric multifunctional molecular probe, 2-(pyren-1-yl)-5-(pyridin-4-yl)thiazolo [5,4-d]thiazole (PYTZ-P) bearing electron-rich pyrene and electron-deficient pyridine units linked through a π-conjugated thiazolo [5,4-d]thiazole (TTz) bridge are reported. Its sensitivity towards protons (TFA) in solution is manifested in the form of bathochromically shifted emission that spreads all over the visible region, and is related to the increased acceptor strength of pyridine upon protonation and subsequent enhanced magnitude of intramolecular charge-transfer in the probe. Similar modulation of the luminescence behaviour of the probe was also observed in the solid state. These observations are well rationalised by the theoretical calculations. The applicability of the sensitivity of the probe towards TFA has been demonstrated by developing the ready-to-use portable paper strips. Furthermore, PYTZ-P showed different acid/base induced absorption/emission switching property. Interestingly, when the response of the probe was noted in the presence of several cations, modulation of the electronic properties was observed only in the presence of Hg2+ ions, with the lowest detection limit of 8.43 × 10-8 M. Additionally, the sensitivity of the probe towards TFA and Hg2+ ions in solution and solid states is convincingly mimicked in the fluorescence imaging of HeLa and A375 cancer cells.

Second-order nonlinear polarizability of "Push-Pull" chromophores. A decade of progress in donor-π-acceptor materials.

Fine tuning and switching of nonlinear optical response of ferrocene chromophores has been an area of considerable significance as evidenced by a large number of reports in the current literature. In this personal account, we present linear/nonlinear behavior and structure-activity relationships of several classes of donor-π-acceptor designs using organometallic and organic materials, developed by our research group during the last decade. The results especially the electronic absorption spectral and the hyper-Rayleigh scattering have been supported by theoretical calculations. Exploiting the redox behavior of ferrocene donor, we have demonstrated switching of quadratic nonlinear optical responses with reversible redox chemistry, which is a useful attribute of nonlinear optical materials. Based on the ease in synthesis, structure diversification and structure-based large and switchable second-order optical nonlinearity, these materials are potential candidates for electro-optic applications.

Quinoline-Dihydropyrimidin-2(1H)-one Hybrids: Synthesis, Biological Activity, and Mechanistic Studies.

A novel class of quinoline-dihydropyrimidin-2(1H)-one (DHPM) hybrids was synthesized and in vitro antiplasmodial activity was evaluated against chloroquine sensitive (D10) and chloroquine resistant (Dd2) strains of Plasmodium falciparum, the human malaria parasite. The antiplasmodial activity was compared to previously reported DHPM based molecular hybrids. Dual mode of antiplasmodial action of the most active member has been evaluated through heme binding study and in silico docking in the active site of dihydrofolate enzymes (wild-type as well as mutant). Favourable pharmacokinetic parameters were predicted in the ADMET evaluation. The new hybrids were also tested against a number of DNA and RNA viruses. No antiviral activity was found, except for one hybrid that showed mild inhibitory activity against two strains of cytomegalovirus (AD-169 and Davis), The most active hybrid was found to be a selective inhibitor of the growth of P. falciparum as well as a modest inhibitor of varicella zoster virus in HEL cells. Cytotoxicity of all hybrids was assessed in HEL, HeLa, Vero, MDCK, and CRFK cell cultures.

Synthesis and antiplasmodial activity of regioisomers and epimers of second-generation dual acting ivermectin hybrids.

With its strong effect on vector-borne diseases, and insecticidal effect on mosquito vectors of malaria, inhibition of sporogonic and blood-stage development of Plasmodium falciparum, as well as in vitro and in vivo impairment of the P. berghei development inside hepatocytes, ivermectin (IVM) continues to represent an antimalarial therapeutic worthy of investigation. The in vitro activity of the first-generation IVM hybrids synthesized by appending the IVM macrolide with heterocyclic and organometallic antimalarial pharmacophores, against the blood-stage and liver-stage infections by Plasmodium parasites prompted us to design second-generation molecular hybrids of IVM. Here, a structural modification of IVM to produce novel molecular hybrids by using sub-structures of 4- and 8-aminoquinolines, the time-tested antiplasmodial agents used for treating the blood and hepatic stage of Plasmodium infections, respectively, is presented. Successful isolation of regioisomers and epimers has been demonstrated, and the evaluation of their in vitro antiplasmodial activity against both the blood stages of P. falciparum and the hepatic stages of P. berghei have been undertaken. These compounds displayed structure-dependent antiplasmodial activity, in the nM range, which was more potent than that of IVM, its aglycon or primaquine, highlighting the superiority of this hybridization strategy in designing new antiplasmodial agents.