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This study presents a series of coumarin nitric oxide donor hybrids that were synthesized, and characterized using FT-IR, H NMR, C NMR, and HR-MS techniques. Initial screening for anti-tubercular activity was conducted against Mycolicibacterium smegmatis MC2155 (M.smeg) under both nutrient-rich and nutrient-poor conditions. Under nutrient-rich conditions, little inhibition was observed. However, four compounds (1e, 2o, 3f, and 5e) demonstrated notable antiproliferative activity under nutrient-poor conditions, with inhibition rates exceeding 95 % at a 50 μM concentration. Subsequent testing of these compounds on Mycobacterium tuberculosis (M.tb) under nutrient-rich conditions showed inhibition rates ranging from 11 % to 37 % at 50 μM. These results indicate that the coumarin nitric oxide donor hybrids are potentially effective in nutrient-limited environments, similar to the intracellular conditions faced by M.tb. In silico cytotoxicity predictions, compared with rifampicin, indicated potentially low toxicity for these compounds. Further optimization and studies are needed to enhance their efficacy under normal conditions, which could lead to the development of new therapeutic strategies against tuberculosis.

Neurodegenerative disorders (NDs) include a range of chronic conditions characterized by progressive neuronal loss, leading to cognitive, motor, and behavioral impairments. Common examples include Alzheimer’s disease (AD) and Parkinson’s disease (PD). The global prevalence of NDs is on the rise, imposing significant economic and social burdens. Despite extensive research, the mechanisms underlying NDs remain incompletely understood, hampering the development of effective treatments. Excitotoxicity, particularly glutamate-mediated excitotoxicity, is a key pathological process implicated in NDs. Targeting the N-methyl-D-aspartate (NMDA) receptor, which plays a central role in excitotoxicity, holds therapeutic promise. However, challenges, such as blood–brain barrier penetration and adverse effects, such as extrapyramidal effects, have hindered the success of many NMDA receptor antagonists in clinical trials. This review explores the molecular mechanisms of NMDA receptor antagonists, emphasizing their structure, function, types, challenges, and future prospects in treating NDs. Despite extensive research on competitive and noncompetitive NMDA receptor antagonists, the quest for effective treatments still faces significant hurdles. This is partly because the same NMDA receptor that necessitates blockage under pathological conditions is also responsible for the normal physiological function of NMDA receptors. Allosteric modulation of NMDA receptors presents a potential alternative, with the GluN2B subunit emerging as a particularly attractive target due to its enrichment in presynaptic and extrasynaptic NMDA receptors, which are major contributors to excitotoxic-induced neuronal cell death. Despite their low side-effect profiles, selective GluN2B antagonists like ifenprodil and radiprodil have encountered obstacles such as poor bioavailability in clinical trials. Moreover, the selectivity of these antagonists is often relative, as they have been shown to bind to other GluN2 subunits, albeit minimally. Recent advancements in developing phenanthroic and naphthoic acid derivatives offer promise for enhanced GluN2B, GluN2A or GluN2C/GluN2D selectivity and improved pharmacodynamic properties. Additional challenges in NMDA receptor antagonist development include conflicting preclinical and clinical results, as well as the complexity of neurodegenerative disorders and poorly defined NMDA receptor subtypes. Although multifunctional agents targeting multiple degenerative processes are also being explored, clinical data are limited. Designing and developing selective GluN2B antagonists/modulators with polycyclic moieties and multitarget properties would be significant in addressing neurodegenerative disorders. However, advancements in understanding NMDA receptor structure and function, coupled with collaborative efforts in drug design, are imperative for realizing the therapeutic potential of these NMDA receptor antagonists/modulators.

Abstract Background Various regulatory authorities are experiencing backlogs of applications which result in delayed access to medicines for patients. The objective of this study is to critically assess the registration process utilised by SAHPRA between 2011 and 2022 and determine the fundamental root causes for the formation of a backlog. The study also aims to detail the remedial actions that were undertaken which resulted in the development of a new review pathway termed the risk-based assessment approach for regulatory authorities experiencing backlogs to implement. Methods A sample of 325 applications was used to evaluate the end-to-end registration process employed for the Medicine Control Council (MCC) process between 2011 and 2017; 129 applications were used for the backlog clearance project (BCP) between 2019 and 2022; 63 and 156 applications were used for the risk-based assessment (RBA) pilot studies in 2021 and 2022, respectively. The three processes are compared, and the timelines are discussed in detail. Results The longest median value of 2092 calendar days was obtained for the approval times between 2011 and 2017 using the MCC process. Continuous process optimisation and refinement are crucial to prevent recurring backlogs and hence implementation of the RBA process. Implementation of the RBA process resulted in a shorter median approval time of 511 calendar days. The finalisation timeline by the Pharmaceutical and Analytical (P&A) pre-registration Unit, which conducts the majority of the evaluations, is used as a tool for the direct comparison of the processes. The finalisation timeline for the MCC process was a median value of 1470 calendar days, the BCP was 501 calendar days and the RBA process phases 1 and 2 were 68 and 73 calendar days, respectively. The median values of the various stages of the end-to-end registration processes are also analysed in order to build efficiency within the process. Conclusions The observations from the study have identified the RBA process which can be implemented to reduce regulatory assessment times while assuring the timeous approval of safe and effective, quality medicines. The continuous monitoring of a process remains one of the critical tools required to ensure the effectiveness of a registration process. The RBA process also becomes a better alternative for generic applications that do not qualify to undergo the reliance approach due to its drawbacks. This robust procedure can therefore be utilised by other regulatory agencies that may have a backlog or want to optimise their registration process.

Background The aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit. Methods There were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P). Results A total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined. Conclusions The overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.

Like much of the developing world, sub-Saharan Africa (SSA) is facing a major challenge. This challenge is due to noncommunicable diseases (NCDs) whose rates are rising dramatically in SSA. Two conditions that frequently coexist head the list of NCDs as either established disease entities or risk factors for NCDs. These are hypertension and diabetes. Hypertension is the foremost cardiovascular condition. The objective of this scoping review is to examine peer-reviewed publications for the period 2009–2019 related to the detection and management of hypertension in SSA. We seek to define the issues confronted in managing hypertension in SSA, what measures have been implemented and evaluated, and what barriers and facilitators have been found. By mapping the complex, heterogeneous literature, we aim to identify the key concepts that underpin a major public health issue in SSA. The central question that this review addresses is how to control hypertension in SSA.

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer’s disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD’s complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;µM. Significant neuroprotective effects towards MPP+-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 µM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection.

Abstract Background Cardiovascular disease (CVD) is the leading cause of mortality in India. Social and behavioural factors are strongly interrelated in the prevention and control of CVD. The ability to make lifestyle changes to control hypertension and diabetes (major risk factors for CVD) is determined by factors such as education, gender, caste, poverty, and urbanicity. This study aimed to improve our understanding of the inter-relationship of social and behavioural factors in the management of elevated serum glucose and high blood pressure and co-morbid mental health conditions. Methods A population-based catchment area cross sectional survey was conducted in Kerala, India. Data were collected from residents aged over 30 years (n = 997) using standardized tools and clinical measures. We performed latent class analysis incrementally to extract homogeneous latent classes of individuals based on their responses to social and behavioural risk factors in the survey. Using structural equation models, we assessed the mediating effect of depression and anxiety, and social or behavioural risk factors, on management of high blood pressure and raised serum glucose levels. Results The prevalence of high blood pressure and blood glucose in the sample was 33 and 26% respectively. Latent class analysis found three clusters of risk factors. One had a predominance of behavioural characteristics, another of social risk factors and the third was a low risk group. Age, female sex, and marital status had an effect on high blood pressure and high glucose, though were mediated by mental health, social and behavioural risk factors. Conclusions Interventions to improve the management of risk factors for CVD need to address social risk factors and be sensitive to the needs of population sub-groups that may require additional support to access health services. An integration of social and health services may be required to achieve this.

A series of multi-target directed edaravone derivatives bearing N-benzyl pyridinium moieties were designed and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects and N-benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheral anionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edaravone-N-benzyl pyridinium hybrid compounds were docked within the AChE active site. The results indicated interactions with conserved amino acids (Trp279 in PAS and Trp84 in CAS), suggesting good dual-site inhibitory activity. Significant in vitro AChE inhibitory activities were observed for selected compounds (IC50: 1.2–4.6 µM) with limited butyrylcholinesterase inhibitory activity (IC50’s >160 µM), indicating excellent selectivity towards AChE (SI: 46 – >278). The compounds also showed considerable antioxidant ability, similar to edaravone. In silico studies indicated that these compounds should cross the blood–brain barrier, making them promising lead molecules in the development of anti-Alzheimer’s agents.

Structural analysis and docking studies of three adamantane-linked 1,2,4-triazole N-Mannich bases (1–3) are presented. Compounds 1, 2 and 3 crystallized in the monoclinic P21/c, P21 and P21/n space groups, respectively. Crystal packing of 1 was stabilized by intermolecular C-H⋯O interactions, whereas compounds 2 and 3 were stabilized through intermolecular C-H⋯N, C-H⋯S and C-H⋯π interactions. The energy frameworks for crystal structures of 1–3 were described. The substituent effect on the intermolecular interactions and their contributions were described on the basis of Hirshfeld surface analyses. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibition potential, pharmacokinetic and toxicity profiles of compounds 1–3 were determined using in silico techniques. Molecular docking of the compounds into the 11β-HSD1 active site showed comparable binding affinity scores (−7.50 to −8.92 kcal/mol) to the 11β-HSD1 co-crystallized ligand 4YQ (−8.48 kcal/mol, 11β-HSD1 IC50 = 9.9 nM). The compounds interacted with key active site residues, namely Ser170 and Tyr183, via strong hydrogen bond interactions. The predicted pharmacokinetic and toxicity profiles of the compounds were assessed, and were found to exhibit excellent ADMET potential.

Mycobacterium tuberculosis has developed extensive resistance to numerous antimycobacterial agents used in the treatment of tuberculosis. Insufficient intracellular accumulation of active moieties allows for selective survival of mycobacteria with drug resistance mutations and accordingly promotes the development of microbial drug resistance. Discovery of compounds with new mechanisms of action and physicochemical properties that promote intracellular accumulation, or compounds that act synergistically with other antimycobacterial drugs, has the potential to reduce and prevent further drug resistance. To this end, antimycobacterial activity, mechanism of action, and synergism in combination therapy were investigated for a series of polycyclic amine derivatives. Compound selection was based on the presence of moieties with possible antimycobacterial activity, the inclusion of bulky lipophilic carriers to promote intracellular accumulation, and previously demonstrated bioactivity that potentially support inhibition of efflux pump activity. The most potent antimycobacterial demonstrated a minimum inhibitory concentration (MIC99) of 9.6 μM against Mycobacterium tuberculosis H37Rv. Genotoxicity and inhibition of the cytochrome bc1 respiratory complex were excluded as mechanisms of action for all compounds. Inhibition of cell wall synthesis was identified as a likely mechanism of action for the two most active compounds (14 and 15). Compounds 5 and 6 demonstrated synergistic activity with the known Rv1258c efflux pump substrate, spectinomycin, pointing to possible efflux pump inhibition. For this series, the nature of the side chain, rather than the type of polycyclic carrier, seems to play a determining role in the antimycobacterial activity and cytotoxicity of the compounds. Contrariwise, the nature of the polycyclic carrier, particularly the azapentacycloundecane cage, appears to promote synergistic activity. Results point to the possibility of combining an azapentacycloundecane carrier with a side chain that promotes antimycobacterial activity to develop dual acting molecules for the treatment of Mycobacterium tuberculosis.

Objectives The purpose of this study is to examine the existing literature of the major social risk factors which are associated with diabetes, hypertension and the comorbid conditions of depression and anxiety in India.Design Scoping review.Data sources Scopus, Embase, CINAHL Plus, PsycINFO, Web of Science and MEDLINE were searched for through September 2019.Eligibility criteria for selecting studies Studies reporting data on social risk factors for diabetes or hypertension and depression or anxiety in community-based samples of adults from India, published in English in the 10 years to 2019, were included. Studies that did not disaggregate pooled data from other countries were excluded.Data extraction and synthesis Two independent reviewers extracted study aims; methods; sample size and description; demographic, social and behavioural risk factors and a summary of findings from each paper. Risk factors were synthesised into six emergent themes.Results Ten studies were considered eligible and included in this review. Nine presented cross-sectional data and one was a qualitative case study. Six themes emerged, that is, demographic factors, economic aspects, social networks, life events, health barriers and health risk behaviours.Conclusions Literature relating to the major social risk factors associated with diabetes, hypertension and comorbid depression and anxiety in India is sparse. More research is required to better understand the interactions of social context and social risk factors with non-communicable diseases and comorbid mental health problems so as to better inform management of these in the Indian subcontinent.

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound 2 crystallizes in the triclinic P-1 space group, while compounds 1 and 3 crystallize in the same monoclinic P21/c space group. Since the only difference between them is the para substitution on the aryl group, the electronic nature of these NO2 and halogen groups seems to have no influence over the formation of the solid. However, a probable correlation with the size of the groups is not discarded due to the similar intermolecular disposition between the NO2/Cl substituted molecules. Despite the similarities, CE-B3LYP energy model calculations show that pairwise interaction energies vary between them, and therefore the total packing energy is affected. HOMO-LUMO calculated energies show that the NO2 group influences the reactivity properties characterizing the molecule as soft and with the best disposition to accept electrons. Further, in silico studies predicted that the compounds might be able to inhibit the 11β-HSD1 enzyme, which is implicated in obesity and diabetes. Self- and cross-docking experiments revealed that a number of non-native 11β-HSD1 inhibitors were able to accurately dock within the 11β-HSD1 X-ray structure 4C7J. The molecular docking of the adamantane-linked 1,2,4-triazoles have similar predicted binding affinity scores compared to the 4C7J native ligand 4YQ. However, they were unable to form interactions with key active site residues. Based on these docking results, a series of potentially improved compounds were designed using computer aided drug design tools. The docking results of the new compounds showed similar predicted 11β-HSD1 binding affinity scores as well as interactions to a known potent 11β-HSD1 inhibitor.

The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes. In the present study, we investigated novel 4-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives for their cytotoxicity, neuroprotective effects via attenuation of MPP+-induced neurotoxicity and calcium influx inhibition abilities through the NMDA receptor and VGCC using neuroblastoma SH-SY5Y cells. All compounds, in general, showed low or no toxicity against neuroblastoma cells at 10–50 µM concentrations. At 10 µM, all compounds significantly attenuated MPP+-induced neurotoxicity as evident by the enhancement in cell viability between 23.05 ± 3.45% to 53.56 ± 9.29%. In comparison to known active compounds, the derivatives demonstrated mono or dual calcium modulating effect on the NMDA receptor and/or VGCC. Molecular docking studies using the NMDA receptor protein structure indicated that the compounds are able to bind in a comparable manner to the crystallographic pose of MK-801 inside the NMDA ion channel. The biological characteristics, together with results from in silico studies, suggest that these compounds could act as neuroprotective agents for the purpose of halting or slowing down the degenerative processes in neuronal cells.

Mycobacterial efflux pumps play a major role in the emergence of antimycobacterial drug resistance. Of particular interest is the proteinaceous multi-drug efflux pump protein Rv1258c that encodes a tetracycline/aminoglycoside resistance (TAP-2)-like efflux pump which is active in susceptible and drug resistant Mycobacterium tuberculosis. Rv1258c is implicated in drug resistance to numerous antimycobacterials including first line drugs rifampicin and isoniazid as well as fluoroquinolone and aminoglycoside antibiotic classes. To date, compounds like verapamil and piperine have been shown to inhibit Rv1258c but no direct evidence for binding or mode of action exist. Therefore in the present study we generated an accurate 3D model of Rv1258c using MODELLER and validated its structure using molecular dynamic simulation studies with GROMACS software. The 3D-structures of Rv1258c and the homologous template 1pw4 were simulated within a POPE/POPG lipid bilayer and found to behave similar. Another important finding was the identification of one local energy minima state of the apo protein, which speaks to the flexibility of the protein and will be investigated further. Extraction of one of the open channel conformations of Rv1258c and blind docking of various structurally diverse putative inhibitors and substrates, allowed for the identification of a probable binding site. Spectinamide was found to bind to a different location on the outside surface of the protein suggesting its ability to avoid the efflux channel. We further identified 246 putative compounds that showed higher binding affinity values to Rv1258c compared to piperine and verapamil. Interaction analysis of the top 20 purchasable compounds identified crucial hydrogen bond interactions with Ser26, Ser45 and Glu243 as well as a pi-pi stacking interaction with Trp32 that accounted for the strong affinity of these compounds for Rv1258c. Future studies will entail purchasing a number of compounds for in vitro activity testing against Mycobacterium tuberculosis.

2-(Adamantan-1-yl)-2H-isoindole-1-carbonitrile (1) has been identified as a neurobiological fluorescent ligand that may be used to develop receptor and enzyme binding affinity assays. Compound 1 was synthesized using an optimized microwave irradiation reaction, and crystallized from ethanol. Crystallization occurred in the orthorhombic space group P212121 with unit cell parameters: a = 6.4487(12) Å, b = 13.648(3) Å, c = 16.571(3) Å, V = 1458(5) Å3, Z = 4. Density functional theory (DFT) (B3LYP/6-311++G (d,p)) calculations of 1 were carried out. Results indicated that the optimized geometry was similar to the experimental results, with a root-mean-squared deviation of 0.143 Å. In this paper, frontier molecular orbital energies and net atomic charges are discussed with a focus on potential biological interactions. Docking experiments within the active site of the neuronal nitric oxide synthase (nNOS) protein crystal structure were carried out and analyzed. Important binding interactions between the DFT-optimized structure and amino acids within the nNOS active site were identified that explained the strong NOS binding affinity reported. Fluorescent properties of 1 were studied using aprotic solvents of different polarities. Compound 1 showed the highest fluorescence intensity in polar solvents, with excitation and emission maximum values of 336 nm and 380 nm, respectively.

Dengue fever is a major public health concern in many tropical and sub-tropical regions. The development of agents that are able to inhibit the dengue virus (DENV) is therefore of utmost importance. This study focused on the synthesis of dual acting hybrids comprising structural features of known DENV inhibitors, amantadine (1) and benzsulfonamide derivatives. Hybrid compound 3, N-(adamantan-1-yl)-4-[(adamantan-1-yl)sulfamoyl]benzamide, was synthesized by reacting amantadine (1) with 4-(chlorosulfonyl)benzoic acid (2), after optimization, in a 2:1 ratio under microwave irradiation conditions in a one-pot reaction. Mono-adamantane derivatives 6 and 7 were synthesised via acyl halide formation of benzoic acid (4) and 4-sulfamoyl benzoic acid (5), respectively, followed by conjugation with amantadine (1) through a conventional or microwave irradiation assisted nucleophilic addition/substitution reaction. The use of microwave irradiation lead to significant increases in yields and a reduction in reaction times. Nuclear magnetic resonance, infra-red and mass spectral data confirmed the structures. Compound 3 and 7 showed significant anti-DENV serotype 2 activity (IC50 = 22.2 µM and 42.8 µM) and low cytotoxicity (CC50 < 100 µM). Possible mechanisms of action are also proposed, which are based on the biological results and molecular docking studies.

In order to utilize the neuroprotective properties of polycyclic cage compounds, and explore the NO-donating ability of nitrophenyl groups, an array of compounds was synthesized where the different nitrophenyl groups were appended on oxa and aza-bridged cage derivatives. Biological evaluations of the compounds were done for cytotoxicity, neuroprotective abilities, the inhibition of N-methyl-d-aspartate (NMDA)-mediated Ca2+ influx, the inhibition of voltage-mediated Ca2+ influx, and S-nitrosylation abilities. All of the compounds showed low toxicity. With a few exceptions, most of the compounds displayed good neuroprotection and showed inhibitory activity for NMDA-mediated and voltage-gated calcium influx, ranging from high (>70%) to low (20–39%) inhibition. In the S-nitrosylation assay, the compounds with the nitro moiety as the NO-donating group exhibited low to good nitrosylation potency compared to the positive controls. From the biological evaluation of the tested compounds, it was not possible to obtain a simple correlation that could explain the results across all of the biological study domains. This can be ascribed to the independent processes evaluated in the different assays, which reiterate that neuroprotection is a result of multifactorial biochemical mechanisms and interactions. However, these results signify the important aspects of the pentacylcoundecylamine neuroprotectants across different biological study realms.

A medium-throughput screen using Mycobacterium tuberculosis H37Rv was employed to screen an in-house library of structurally diverse compounds for antimycobacterial activity. In this initial screen, eleven 7-substituted coumarin derivatives with confirmed monoamine oxidase-B and cholinesterase inhibitory activities, demonstrated growth inhibition of more than 50% at 50 µM. This prompted further exploration of all the 7-substituted coumarins in our library. Four compounds showed promising MIC99 values of 8.31–29.70 µM and 44.15–57.17 µM on M. tuberculosis H37Rv in independent assays using GAST-Fe and 7H9+OADC media, respectively. These compounds were found to bind to albumin, which may explain the variations in MIC between the two assays. Preliminary data showed that they were able to maintain their activity in fluoroquinolone resistant mycobacteria. Structure-activity relationships indicated that structural modification on position 4 and/or 7 of the coumarin scaffold could direct the selectivity towards either the inhibition of neuronal enzymes or the antimycobacterial effect. Moderate cytotoxicities were observed for these compounds and slight selectivity towards mycobacteria was indicated. Further neuroprotective assays showed significant neuroprotection for selected compounds irrespective of their neuronal enzyme inhibitory properties. These coumarin molecules are thus interesting lead compounds that may provide insight into the design of new antimicrobacterial and neuroprotective agents.