INTRODUCTION:The global increase in antimicrobial resistance presents a significant public health challenge and calls for the discovery of new antimicrobial agents with innovative mechanisms of action. Spirocyclic compounds, characterized by two or more rings connected via a single shared atom, have attracted interest due to their rigid three-dimensional structures and promising pharmacological activities. This review aims to summarize research published between 2019 and 2025 on the antibacterial potential of natural, semisynthetic, and synthetic spirocyclic compounds, emphasizing their activity against Gram-positive, Gramnegative, and resistant bacterial strains. It also highlights promising therapeutic scaffolds and explores Structure- Activity Relationships (SAR) where available. METHODS:Relevant literature was gathered from peer-reviewed scientific databases. Studies reporting antibacterial evaluations of spirocyclic derivatives were included. Reported compounds were classified based on their core scaffold type, and their antibacterial activities, synergistic effects with standard antibiotics, and insights from computational docking were examined. RESULTS:Several spirocyclic scaffolds demonstrated antibacterial potential, including spiro β-lactams, spiro chromanes, spiro thiazolidines, and especially spiro oxindoles, which were the most extensively studied (44 research articles). Many compounds showed notable antibacterial activity against drug-resistant strains, and synergistic effects were observed when combined with conventional antibiotics. One spiro pyrimidinetrione derivative was approved recently by the US FDA, indicating translational potential. Molecular docking studies supported mechanistic understanding by predicting possible bacterial targets. DISCUSSION:Due to their wide applications across various scaffolds, spiro frameworks could be a valuable strategy in defeating bacteria. This architecture offers structurally unique compounds by expanding the threedimensional chemical space that may address antimicrobial resistance. Further exploration through Mechanistic validations and systematic structure-activity relationships studies is required to fully understand the potential of spiro compounds. CONCLUSION:Spirocyclic compounds are a valuable class of antibacterial agents owing to their structural diversity and efficacy. This review offers insights into their therapeutic potential and provides a foundation for future drug development targeting antimicrobial resistance.

IntroductionPoly ADP-ribose polymerase 1 (PARP-1) plays a crucial role in the gene repair process and thus attracts significant attention in the development of anti-cancer drugs. Although some FDA-approved compounds, including Olaparib, are effective in BRCA-mutated cancers, they face the obstacle of resistance and adverse reactions. Among these, Arenobufagin, a bufadienolide extracted from Bufo gargarizans, has been shown to be a potential PARP-1 inhibitor. Although the specific process of molecular inhibition is not fully understood, the investigation focused on the binding and molecular interactions between compound 30 and Olaparib to assesstheir potential as a novel PARP-1 inhibitory drug. MethodsMolecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy (BFE) analyses were employed to explore the interactions between the ligands and the protein. Structural stability and key residues involved in the interactions mediated by the ligands were determined through conformational and per-residue energy decomposition (PRED) analyses. ResultsArenobufagin 30 showed a binding affinity of –51.88 kcal/mol, which was similar to that of Olaparib (- 52.99 kcal/mol). This affinity was primarily supported by strong electrostatic and van der Waals interactions. Conformational analysis revealed that arenobufagin 30 induced specific dynamic changes in the PARP-1 molecule without disrupting its secondary structures. PRED showed improved binding with the crucial residues of the catalytic domain, suggesting an unusual mode of stabilization and inhibition. DiscussionThe similarity in binding affinity and unique conformational modification presented by arenobufagin 30 indicates an unconventional PARP-1 inhibitory mechanism. The atomistic information provided for the inhibitory actions of naturally occurring bufadienolides can be used to suggest their potential role in counteracting the limitations presented by existingPARP-1 inhibitors. ConclusionThis study provides mechanistic insight into the inhibition of PARP-1 by Arenobufagin, suggesting it as a candidate for the development of novel anti-PARP-1 agents.

Diabetic foot ulcers are severe complications of diabetes mellitus; they are characterized by chronic inflammation, poor wound healing, and high risks of infection leading to extended hospitalizations and amputation. Although progress has been made in the conventional care of wounds, current therapies still fall short in yielding optimal healing outcomes. In recent years, bioactive natural products and phytochemicals have emerged as promising therapeutic agents due to their diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and pro-angiogenic effects. Key active phytochemicals such as curcumin, quercetin, resveratrol, and berberine have been investigated for their potential to enhance wound closure, modulate immune function, and promote tissue regeneration. A literature review was conducted through a systematic search of electronic databases, including PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar, using keywords such as "diabetic foot ulcers," "phytochemicals," "natural products," "wound healing," and "drug delivery systems." Many phytochemicals have been reported for their efficacy in DFU models, modulating oxidative stress, stimulating fibroblast proliferation, enhancing collagen synthesis, and inhibiting the growth of microbial biofilms. Advanced drug delivery platforms have been developed to improve the solubility, stability, and targeted delivery of these compounds to the site of injury, utilizing hydrogels, nanoparticles, and polymer-based scaffolds. Preclinical and some clinical studies support the therapeutic potential of these agents; however, translational challenges persist due to issues with formulation, standardization, and the need for large-scale clinical validation. Phytochemical-based interventions are, therefore, a promising complementary approach for treating DFUs. The integration of these natural agents into conventional wound care regimens can improve healing outcomes and reduce complications. Future studies should focus on well-designed clinical trials, detailed mechanistic studies, and standardized and scalable delivery systems to support the clinical translation of phytochemical therapies in DFU management.

In this research work, a new series of structurally diverse 2-isobutoxy-5-(thiazol-2-yl)benzonitrile 3a-d and 2-isobutoxy-5-(thiazol-2-yl)benzoic acid derivatives 5a-f were designed, synthesized, and characterized. The structural elucidation of the synthesized novel compounds was carried out using a combination of spectroscopic methods, including FT-IR, 1H and 13C NMR, mass spectrometry, and single-crystal X-ray diffraction. The crystal structure of 3a is stabilized via C-H...N, C-H...Cl and pi...pi interactions. Furthermore, these compounds were investigated for larvicidal activity against Anopheles arabiensis, and the title compounds 5c, 5a, and 3c exhibited larvicidal activity at 81.11, 70, and 66.67 %, respectively, compared with the standard larvicide Temephos. To elucidate the structure-activity relationship and/or mechanism of action, a molecular modelling study was performed, considering six potential larvicidal targets. Among all test compounds, and compared with the standard larvicide (Temephos), compounds 5a and 5c exhibited higher binding affinity and interactions with juvenile hormone-binding protein (5V13) and sterol carrier protein-2 (1PZ4). The docking studies revealed that both 5a and 5c achieved high docking scores along with significant binding energies. Furthermore, molecular dynamics simulations over 300 ns confirmed the stability of these complexes and highlighted key interactions, supporting the potency of these compounds. Evaluation of pharmacokinetic properties demonstrated favorable parameters for 5a and 5c, including an optimal balance between hydrophilicity and lipophilicity, which contributes to improved absorption, distribution, and bioavailability, along with a lower toxicity profile. Thus, these compounds can be considered as promising lead molecules for further optimizations and development as potent larvicidal agents.

A. arabiensis is one of the main vectors of malaria in the African continent. Due to increasing insecticidal resistance, medicinal chemists are searching for new, effective, affordable, and eco-friendly alternative. This study reports the synthesis of DHPP derivatives using the Biginelli multi-component single-pot reaction, i.e., in the presence of ceric ammonium nitrate as an effective catalyst. The larvicidal efficacy against A. arabiensis was first screened for all synthesized DHPPs at a single concentration, after which the most active compounds were further evaluated through dose-response bioassays. All compounds exhibited moderate to excellent toxicity, with percentage mortality increasing from 24 to 48h of exposure. The most promising compounds were 4e, 4h, and 4j, which showed low LC50 and LC90 values compared to the reference larvicide Temephos. Compound 4e consistently demonstrated greater potency than 4j, with lower LC50 and LC90 values and a steeper slope, while 4h showed intermediate activity. Further in silico molecular docking and dynamic studies were evaluated to understand the binding mechanism of the synthesized DHPPs with the target enzyme. These findings highlight DHPP derivatives, particularly compound 4e, as promising candidates for larvicidal development against A. arabiensis.

The rapid emergence of drug-resistant Mycobacterium tuberculosis and other bacterial pathogens has significantly reduced the effectiveness of conventional antimicrobial therapies. Single-target antibiotics are particularly vulnerable to resistance due to mutations, efflux mechanisms, and metabolic adaptation. This review highlights plant-derived secondary metabolites as promising multitarget antimicrobial agents that simultaneously disrupt key bacterial processes, including DNA replication, cell wall biosynthesis, energy metabolism, and virulence regulation. Evidence from experimental and computational studies demonstrates that major phytochemical classes, alkaloids, flavonoids, terpenoids, and phenolics, exhibit multitarget activity by inhibiting DNA gyrase, suppressing efflux pumps, disrupting membrane integrity, and inducing redox imbalance. Notably, compounds such as berberine, quercetin, curcumin, and thymol have been shown to enhance intracellular drug accumulation, inhibit biofilm formation, and restore antibiotic sensitivity in drug-resistant strains. Computational approaches, including molecular docking, molecular dynamics simulations, network pharmacology, and the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling, further support these findings by revealing strong binding affinities, stable ligand–target interactions, and favorable pharmacokinetic properties of selected phytochemicals against critical M. tuberculosis targets such as Enoyl-ACP reductase (InhA) and Decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (DprE1). Thus, these findings demonstrate that plant-derived multitarget inhibitors not only interfere with multiple essential and adaptive bacterial pathways but also reduce the likelihood of resistance development. This positions them as promising candidates for next-generation anti-infective therapies and adjuncts to existing treatment regimens.

Cancer remains one of the leading causes of mortality worldwide, mainly due to its capacity to evade apoptosis, a tightly regulated process essential for maintaining cellular homeostasis. The dysregulation of apoptotic pathways, involving key molecular regulators such as caspases, Bcl-2 family proteins, and inhibitor of apoptosis proteins (IAPs), contributes to cancer progression and therapeutic resistance. This review provides a comprehensive overview of apoptosis's intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways, distinguishing them from necrotic cell death and highlighting their roles in tumour suppression. Amid growing interest in alternative and adjunctive therapies, medicinal plants have emerged as a rich source of bioactive compounds capable of selectively modulating apoptosis in cancer cells. We explore the therapeutic potential of phytochemicals, including alkaloids, flavonoids, terpenoids, and phenolics that exhibit pro-apoptotic activity across diverse cancer models. Special attention is given to the synergistic effects of plant-derived compounds in crude extracts and their combinatorial use with conventional chemotherapeutics, which may enhance efficacy and reduce toxicity. By integrating mechanistic insights with preclinical findings, this review underscores the strategic promise of plant-based agents in modern oncology. Incorporating natural products into cancer therapy represents a novel and rational therapeutic approach. We also address challenges such as compound standardization, bioavailability, and mechanistic validation, while proposing future directions for research to unlock the full potential of phytotherapy in precision cancer medicine.

A series of sixteen ethyl 3-(4-substitutedbenzoyl)-7-methoxyindolizine-1-carboxylate derivatives (1a-1p) were assessed for their larvicidal study against Anopheles arabiensis using a standard WHO larvicidal assay, with Temephos (4 mu g/mL) as the standard, to evaluate the nature of substitutions on the indolizine pharmacophore. Compounds 1h and 1l demonstrated excellent larvicidal activity at 48 h, achieving mean mortality rates of 98 % and 80 %, respectively, while the other compounds showed lower to moderate activity. Additionally, we report two single crystal structures of 1i and 1m from this series to investigate their structural characteristics. To establish a plausible mechanism of action and correlate it with the observed larvicidal activity, we employed computational approaches, including molecular docking and molecular dynamics simulations, to identify potential targets for the compound series. The results revealed that compounds 1h and 1l exhibited strong binding affinities with PDB ID: 6ARY (acetylcholinesterase mutant from the malaria vector) and PDB ID: 4JBV (calciumdependent protein kinase 1). Their strong binding affinities align with their observed larvicidal effectiveness. The stability of the protein-ligand complexes was further validated from molecular dynamics insights through RMSD, RMSF, hydrogen bond analysis, and 2D interaction plots. In addition, ADMET predictions highlighted compounds 1h and 1l as promising candidates, providing a foundation for the development of novel larvicidal agents.

Momordica spp. has been traditionally used to manage type 2 diabetes mellitus, but the mechanisms and metabolites remain unclear. This study evaluated the inhibitory potential of Momordica balsamina extracts on α-amylase and α-glucosidase in vitro, identifying cucurbitacin I and momordin Ic via high-performance liquid chromatography-photo diode array, and their inhibitory potential in silico. Ethyl acetate seed extract (14.46 µg/ml) and hexane fruit flesh extract (16.79 µg/ml) exhibited lower IC50 values against α-amylase and α-glucosidase, respectively, compared to acarbose (reference standard). Comparatively, momordin Ic concentrations (36.57-605.98 µg/ml) were higher than cucurbitacin I (17.08-44.34 µg/ml). A 140 ns simulation showed that cucurbitacin I (-63.06 kcal/mol) and momordin Ic (-66.53 kcal/mol) exhibited stronger binding to α-amylase than acarbose (-36.46 kcal/mol), whereas cucurbitacin I (-38.08 kcal/mol) and momordin Ic (-54.87 kcal/mol) displayed weaker binding to α-glucosidase, relative to acarbose (-63.73 kcal/mol). Generally, momordin Ic demonstrated better thermodynamic properties, hence further in vitro and in vivo studies are needed to validate their antidiabetic potential.

A series of novel ethyl 3-benzoyl-7-(4-nitrobenzyl) indolizine-1-carboxylate (4a-g) and diethyl 3-(4-bromobenzoyl)-7-(4-nitrobenzyl) indolizine-1,2-dicarboxylate (4h and 4i) derivatives were synthesized and biologically assayed against Anopheles arabiensis, a malaria vector, following standard WHO larvicidal assay protocols. Among these, compounds 4c and 4e exhibited the highest potency, achieving mortality rates of 65.56 +/- 3.39 %. Although their efficacy was lower than the reference compound Temephos, these findings together with their physicochemical and pharmacokinetic profiles indicate their potential as lead candidates for more effective larvicidal agents. The structural novelty of 4c and 4e lies in the indolizine core with fluorine 4c and chlorine 4e substitutions, which differentiate them from traditional larvicidal compounds. These modifications enhance lipophilicity, potentially improving absorption and interaction with biological membranes. In silico studies were performed to understand the mechanisms of action, including molecular docking with six probable larvicidal targets. Among these, the targeted proteins 4JBV and 6ARY, revealed strong binding affinities and correlation with the larvicidal activities of our tested compounds, including the most active compounds 4c and 4e compared to Temephos. Molecular dynamics simulations validated that both compounds maintained stable complex formation, as evidenced by RMSD (<2 & Aring;), RMSF, H-bond plots, etc. Additionally, in silico ADMET profiling assessed the pharmacokinetic properties of these compounds, revealing that 4c and 4e exhibited favorable ADME parameters (e.g. high intestinal absorption, >94 %), and acceptable toxicity levels and no Pan-Assay Interference Compounds (PAINS) alerts, indicating strong larvicidal target specificity. Their moderate synthetic accessibility (3.14 - 3.15) supports that further structural modifications could enhance their potency in anti-malarial vector agent development. Overall, the integration of promising larvicidal activity, stable target interactions, and favorable pharmacokinetics highlights the potential of 4c and 4e in the development of novel anti-malarial agents. Future studies should focus on optimizing their structural framework to enhance efficacy, providing valuable contributions to malarial vector control strategies.

Abstract Hypoxis hemerocallidea, a medicinal plant traditionally used for its therapeutic properties, has demonstrated potential anticancer activity in vitro. This study evaluated the cytotoxic and pro-apoptotic effects of methanol (MeOH) and aqueous extracts of H. hemerocallidea on A375 melanoma, MCF-7 breast cancer, and HEK293 normal cell lines. MTT assays revealed concentration-dependent inhibition of cancer cell proliferation, with IC50 values of 44.82–63.1 µg/mL for MeOH extract and 55.02–57.6 µg/mL for aqueous extract, while sparing normal HEK293 cells. Morphological analysis showed characteristic apoptotic changes, including cell shrinkage, rounding, membrane blebbing, and formation of apoptotic bodies. Flow cytometric analysis demonstrated increased caspase-3 activity (13–15% for extracts vs. 47.8% for Doxorubicin) and mitochondrial membrane depolarization (17.4% for aqueous extract, 48.4% for MeOH extract vs. 56.5% for Doxorubicin), indicating activation of intrinsic apoptotic pathways. Collectively, these findings suggest that H. hemerocallidea extracts selectively induce apoptosis in cancer cells through mitochondrial-dependent mechanisms, highlighting their potential as natural anticancer agents. Further studies are warranted to isolate active compounds and elucidate their molecular targets.

A series of novel dichloroindolizine carboxylate analogues (4a-n) have been prepared by using 3,5-dichloropyridine, and substituted phenacyl bromide with electron-deficient acetylene via a [3 + 2] cycloaddition reaction. This methodology features a reaction that is free from transition metal or catalyst, providing an eco-friendly synthesis for developing dichloroindolizines. All the synthesized products (4a-n) were characterized by 1H NMR,13C NMR, and HRMS spectroscopic techniques. All the final compounds were evaluated for larvicidal activity using Temephos as the reference standard against Anopheles arabiensis. Compound 4c exhibited the highest larval mortality of 96.67% after 48 h of exposure, which is on par with the positive control, Temephos. Compounds 4e, 4i, 4j, and 4m were moderately toxic, resulting in 70.00%, 74.44%, 73.33%, and 70.00% mortality, respectively, after 48 h of exposure. To validate the biological activity and elucidate a plausible mechanism of action of these compounds molecular docking studies were carried out against six known antimalarial targets. Potential compounds 4c and 4e showed significant binding affinities and correlation of larvicidal activity against the targets calcium-dependent protein kinase-1 (4JBV) and acetylcholinesterase from malaria vector (6ARY). Molecular dynamics studies (300 ns) further supported the stability of these compounds 4c and 4e inside the binding pockets of 4JBV and 6ARY, as evidenced by the RMSD, RMSF, H-bonding, and other stable interactions. Therefore, these novel indolizines can be considered as potential multi-targeting lead molecules for further optimization to combat malaria.

A series of ester derivatives of (6-methyl-4-phenyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidin-5-yl)(piperidin-1-yl) methanone (6a-6k) have been synthesized using a solvent and catalyst-free one-pot two-step synthetic method. These 11 molecules have been characterized by spectroscopic techniques such as FT-IR, NMR (1H and 13C), and single-crystal x-ray structural analysis. The Hirshfeld surface and 2D fingerprint plot elucidated the intermolecular interactions and their contribution to crystal packing. Furthermore, the computational calculations, such as FMOs and MEP, revealed the global reactivity descriptors and sites for noncovalent interactions, such as hydrogen bonding, respectively, in these pharmacophores. Among these derivatives, the 6h molecule, which bears -CF3 on the phenyl ring, has piperidine substitution on the ester group and contains a thiourea moiety, demonstrated the best larvicidal activity against Anopheles arabiensis, achieving a 94% mortality rate compared to the standard sample Temephos (98%).

A novel series of 7-(trifluoromethyl)indolizine derivatives (4a-4n) was synthesized using a 1,3-Dipolar cycloaddition reaction. Structure elucidation of the synthesized compounds was done using various spectroscopic techniques. Compounds were assessed for their larvicidal activity against Anopheles arabiensis. Exposure of Anopheles arabiensis larvae to a series of 7-(trifluoromethyl)indolizine at 4 µg/mL for 24 and 48 h resulted in moderate to high larval mortality rates. Among them, compounds 4b, 4a, 4g, and 4m exhibited the most promising larvicidal activities, with mortality rates of 94.4

The diethyl 3-(4-substitutedbenzoyl)indolizine-1,2-dicarboxylates have been synthesized by reacting the electron-deficient diethyl but-2-ynedioate with 1-(2-(4-substitutedphenyl)-2-oxoethyl)pyridin-1-ium bromide, the intermediates obtained from the reaction of pyridine and 4-substituted phenacyl bromides. The synthesized compounds were investigated by FT-IR, NMR (1H and 13C), LC-MS, and elemental analysis spectroscopic methods along with PXRD. The molecular structures were determined using the single crystal X-ray diffraction technique which revealed that 5a and 5c crystallize in triclinic space group P1¯. The crystal structures of 5a and 5c preferred the C-H···O hydrogen-bonded dimeric ring motifs, resembling those observed in the earlier reported 5b. Furthermore, various computational analyses such as Hirshfeld surface, Energy framework, and MEP analysis predicted the interaction site and inter-molecular interactions in these molecules. The FMOs analysis was carried out to obtain global reactivity parameters for the synthesized compounds (5a-c). The NCI and QTAIM studies revealed the nature as well as qualitative and quantitative description of intra and inter-molecular hydrogen bonding interactions present in these molecules and their crystal packing.

According to WHO, in 2021, there was an estimation of 247 million malaria cases from 84 malaria-endemic countries. Globally an estimated count of 2 billion malaria cases and 11.7 million deaths due to malaria were recorded in the past two decades. Further, the emergence of drug-resistant mosquitos threatens mankind. Therefore, the development of newer larvicidal agents is the need of the hour. This research identifies a new series of variably substituted indolizines for their effectiveness in controlling Anopheles arabiensis larvae through larvicidal activity. The series of Ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues (4a-j) were synthesized by reacting 4-(piperidin-1-yl)pyridine, phenacyl bromides with ethyl propiolate via 1, 3-dipolar cycloaddition and the green metrics of the process are reported. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1H NMR,13C NMR, FT-IR, and HRMS. The larvicidal effectiveness of the newly synthesized compounds was assessed against Anopheles arabiensis. Among the compounds studied, namely 4c, 4d, 4e, and 4f, displayed the most notable larval mortality rates within the series, reaching 73%, 81%, 76%, and 71% respectively, in contrast with the negative control acetone. In comparison, the standard Temephos exhibited a mortality rate of 99% at the same concentration. Furthermore, computational approaches including molecular docking and molecular dynamics simulations identified the potential targets of the series compounds as the larval Acetylcholinesterase (AChE) enzyme and the Sterol Carrier Protein-2 (SCP-2) protein. However, it is essential for these computational predictions to undergo experimental validation.

In the current study, two sets of compounds: (E)-1-(2-(4-substitutedphenyl)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium derivatives (3a-3e); and (E)-3-(substitutedbenzoyl)-7-((hydroxyimino)methyl)-2-substitutedindolizine-1-carboxylate derivatives (5a-5j), were synthesized and biologically evaluated against two strains of Mycobacterial tuberculosis (ATCC 25177) and multi-drug resistant (MDR) strains. Further, they were also tested in vitro against the mycobacterial InhA enzyme. The in vitro results showed excellent inhibitory activities against both MTB strains and compounds 5a-5j were found to be more potent, and their MIC values ranged from 5 to 16 μg/mL and 16-64 μg/mL against the M. tuberculosis (ATCC 25177) and MDR-TB strains, respectively. Compound 5h with phenyl and 4-fluorobenzoyl groups attached to the 2- and 3-position of the indolizine core was found to be the most active against both strains with MIC values of 5 μg/mL and 16 μg/mL, respectively. On the other hand, the two sets of compounds showed weak to moderate inhibition of InhA enzyme activity that ranged from 5 to 17 % and 10-52 %, respectively, with compound 5f containing 4-fluoro benzoyl group attached to the 3-position of the indolizine core being the most active (52 % inhibition of InhA). Unfortunately, there was no clear correlation between the InhA inhibitory activity and MIC values of the tested compounds, indicating the probability that they might have different modes of action other than InhA inhibition. Therefore, a computational investigation was conducted by employing molecular docking to identify their putative drug target(s) and, consequently, understand their mechanism of action. A panel of 20 essential mycobacterial enzymes was investigated, of which β-ketoacyl acyl carrier protein synthase I (KasA) and pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (BioA) enzymes were revealed as putative targets for compounds 3a-3e and 5a-5j, respectively. Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization.

Malaria is one of the most known vector-borne diseases caused by female Anopheles mosquito bites. According to WHO, about 247 million cases of malaria and 619,000 deaths were estimated worldwide in 2021, of which 95% of the cases and 96% of deaths occurred in the African region. Sadly, about 80% of all malaria deaths were of children under five years old. Despite the availability of different insecticides used to control this disease, the emergence of drug-resistant mosquitoes threatens public health. This, in turn, highlighted the need for new larvicidal agents that are effective at different larval life stages. This study aimed to identify novel larvicidal agents. To this end, a series of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates 8a-i was synthesized using a three-step chemical synthetic approach via a Biginelli reaction employed as a key step. All title compounds were screened against Anopheles arabiensis to determine their larvicidal activities. Among them, two derivatives, ethyl 2-((4-bromophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8b and ethyl 2-((4-bromo-2-cyanophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8f, showed the highest larvicidal activity, with mortality of 94% and 91%, respectively, and emerged as potential larvicidal agents. In addition, computational studies, including molecular docking and molecular dynamics simulations, were carried out to investigate their mechanism of action. The computational results showed that acetylcholinesterase appears to be a plausible molecular target for their larvicidal property.Communicated by Ramaswamy H. Sarma.

Malnutrition is a global issue that affects both children and adults irrespective of their socio-economic status. It is therefore important to find various means to tackle malnutrition. This is especially important as undernutrition and overnutrition can be linked to a variety of non-communicable diseases (NCDs). Therefore, this study aimed to gather more insight into the nutritional and phytochemical quality of Momordica balsamina leaves and fruit (fruit pericarp, fruit flesh and seeds). The results showed that M. balsamina had a nutritional composition that would be advantageous to the human diet. The nutritional quality was verified by the presence of a high protein percentage across all samples (19.72–29.08%), with the leaves containing the highest protein content (29.08% ± 0.77). There was also a low-fat content present across all samples which ranged from 1.03% to 2.40%. The ash content indicated the presence of total minerals to be adequate (2.93–21.16%), where the pericarp had the highest ash quantity (21.16% ± 0.09). Overall, the moisture levels were low (7.11–13.40%); with M. balsamina seeds containing the highest carbohydrate content (67.84% ± 0.30). Moreover, rich in the major phytoconstituents, M. balsamina extracts were found to contain alkaloids, saponins, cardiac glycosides, steroids and triterpenoids. Based on these findings, it can be deduced that the incorporation of M. balsamina into an individual’s diet could prevent diseases associated with malnutrition and could be used to supplement the human diet in managing certain NCDs.