Six novel chalcone-derived thiosemicarbazones (L1-L6) were synthesised and characterised by FT-IR, DSC, elemental CHNS analysis, Q-TOF LC/MS, H-1 and C-13 NMR spectroscopy, with the structure of L3 further confirmed by single-crystal X-ray crystallography. In vitro evaluation against chloroquine-sensitive P. falciparum (3D7 strain) revealed potent antimalarial activity (IC50 = 6.0-205.1 & micro;M), with L4 exhibiting the highest potency (IC50 = 6.0 & micro;M). Cytotoxicity screening revealed that all compounds were non-toxic to human MRC-5 cells at a concentration of 200 & micro;M. The predicted pharmacokinetic profiles revealed that the superior potency of L4 is underpinned by its high lipophilicity (LogP = 5.7) and low systemic clearance, which likely facilitates parasite penetration and sustained exposure. These results highlight L4 as a promising antimalarial lead compound worthy of further development.

This study investigated the insecticidal activity of three phenylpropanoids-asaricin (1), isoasarone (2), and trans-asarone (3)-isolated from the aerial parts of Piper sarmentosum against adult mosquito vectors: Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Bioassay-guided fractionation of the plant's hexane extract led to the isolation of these phenylpropanoids. Compounds 1 and 2 exhibited strong adulticidal effects against Aedes species, with LD₅₀ values ≤ 8.8 µg/mL and LT₅₀ values ≤ 29 min. Meanwhile, Culex quinquefasciatus was less susceptible to these compounds, showing LT₅₀ values ≤ 56 min. In contrast, compound 3 showed moderate toxicity across all species. To explore the potential resistance mechanism, glutathione S-transferase (GST) activity was measured and found to correlate positively with the LD₉₅ values of the compounds. Mosquitoes exposed to all isolated phenylpropanoids at LD₉₅ levels showed a significant increase in GST activity, suggesting its involvement in detoxification. Molecular docking studies further confirmed this interaction, revealing consistent binding of all three compounds to key residues (PRO11, GLU64, SER65, ARG66, and TYR105) within the GST active site. Despite increased GST activity-a known marker of metabolic resistance- compounds 1 and 2 remained highly effective, indicating that their mode of action may overcome or bypass common resistance pathways. These findings highlight the potential of P. sarmentosum-derived phenylpropanoids as promising botanical insecticides and underscore the importance of understanding enzyme-ligand interactions in developing effective mosquito control strategies.

A comprehensive 13C NMR-based dereplication and LC-MS/MS based-molecular networking analyses were performed on the bark extract of Xylopia ferruginea (Hook.f. Thomson) and led to the discovery of fifteen isoquinoline alkaloids; lysicamine (1), liriodenine (2), O-methylmoschatoline (3), anonaine (4), norlirioferine (5), isoboldine (6), columbamine (7), jatrorrhizine (8), palmatine (9), nuciferine (10), roemerine (11), N-methylasimilobine (12), N-methylasimilobine N-oxide (13), stephanine (14) and isocorydine (15). Further purification led to the isolation of one new compound, 4,5-dihydro-2-hydroxy-1-methoxy-7H-dibenzo[de,g]quinolin-7-one (16), and four known compounds; lysicamine (1), liriodenine (2), nuciferine (10) and roemerine (11). Selected alkaloid isolates were evaluated for neuroprotective activity in a transgenic Caenorhabditis elegans model expressing human amyloid-beta (Aβ). Lysicamine (1) and liriodenine (2), exhibited moderate neuroprotective activity with paralysis delayed by 1.1 h and 0.5 h, respectively. This study highlights the chemical profile and neuroprotective activity of isoquinoline alkaloids from X. ferruginea and underscores the utility of integrative dereplication and molecular networking approaches in natural product discovery.

alpha,beta-Dibromo compounds are important intermediates in the synthesis of epoxides and 1,2-diols. They can alpha-functionalization ketones to form electrophilic atoms for subsequent substitution reactions. However, conventional bromination methods often involve hazardous solvents, prolonged reaction times and generate chemical waste. In this study, alpha,beta-dibromoketones 2a and 2b were synthesized from aldol condensation products (1a and 1b) using pyridinium tribromide via a green and solvent-free mechanochemical approach at room temperature. The reactions afford excellent yields of 75 % and 95 %, demonstrating high efficiency and a reduced environmental footprint. Characterisations of these compounds were carried out using 1H and 13C Nuclear Magnetic Resonance (NMR) and high-resolution mass spectrometry (HRMS). This work establishes a green and energy-efficient mechanochemical bromination method, demonstrating the potential of mechanochemistry as an environmentally friendly alternative to traditional halogenation and as an efficient route to construct complex molecular frameworks relevant to pharmaceutical and synthetic chemistry applications.

The hydantoin scaffold is renowned for its wide-ranging biological activities, including antibacterial, antiviral, anticancer, anti-inflammatory, and anticonvulsant effects. In this study, we present an innovative, sustainable approach to synthesizing hydantoins (H2a–j) directly from amino acids. This method employs a column chromatography-free, two-step, one-pot microwave-assisted synthesis that delivers hydantoins in yields ranging from 34% to 89%. The protocol demonstrates exceptional functional group tolerance, accommodating phenyl, aliphatic, phenol, alcohol, heterocyclic, and sulfide groups. This scalable, rapid, and eco-friendly strategy offers a promising avenue for the efficient synthesis of hydantoins, aligning with green chemistry principles and expanding the accessibility of these bioactive compounds for pharmaceutical applications.

In view of the emergence of drug-resistant strains of Plasmodium falciparum, there is an urgent need for the development of new effective antimalarial agents to mitigate the issue of drug resistance. In this study, a series of lupeol (2) and betulin (3) derivatives were synthesised, characterised and evaluated for their antimalarial activity against the P. falciparum FCR3 strain. Eight compounds, including lupenone (1), displayed good anti-plasmodial potency with IC50 values ranging from 0.03-9.9 µM. Moreover, in vitro results showed that compound 1 and derivatives 4a and 4b were the most active compounds with potent inhibitory activity of (0.3 ± 0.3, 0.03 ± 0.05 and 0.7 ± 0.8 μM), respectively, compared to the reference drugs artemisinin and chloroquine (0.7 ± 0.3 and 10.3 ± 2.9 μM), respectively. Furthermore, molecular docking analysis of these compounds revealed good affinity to the binding site of the P. falciparum protein of the PfATP6 with a binding affinity between -9.8 and -8.4 kcal mol-1via multiple hydrophobic interactions with the amino acid of the PfATP6 protein. The results showed hydrogen bonds and various hydrophobic interactions between the studied compounds and the amino acid of the PfATP6 protein, such as ASN1039, VAL984, ILE981 and ILE1041. Therefore, these compounds could be promising lead structures for further validation as potential candidates in developing new antimalarial drugs.

Styryl lactones, which are ubiquitous in the genus Goniothalamus, have emerged as promising candidates in combating cancer due to their ability to inhibit the growth of cancer cells. Therefore, this study aimed to rapidly identify styryl lactones from the bark of a Malaysian plant, Goniothalamus giganteus, by combining conventional phytochemical methods with 13C NMR-based dereplication analysis to speed up the chemical profiling and structural elucidation processes. From the 13C NMR-based dereplication analysis of Goniothalamus giganteus using MixONat software, a total of nineteen compounds were identified; two terpenes (1-2), one flavonoid (3), and sixteen styryl lactones (4-19). Purification exercise led to the isolation of thirteen compounds, including two new compounds possessing a bis-styryllactone skeleton; goniogigantone A (20) and goniogigantone A (21), along with other eleven known compounds (1, 3, 9, 11, 12, 14, 17, 22-25). Altholactone (11), the major compound isolated from this species had showed the highest cytotoxic effect against both H103 and H400 oral squamous cell carcinoma (OSCC) cell lines with IC50 values of 5.68 μM and 5.08 μM, respectively via MTT assay.

In the constantly evolving landscape of higher education, integrating cutting-edge technologies has become crucial for enhancing learning experiences. As advancements in Augmented Reality (AR) and Virtual Reality (VR) continue to redefine educational paradigms, it is essential to understand their unique contributions to Chemistry education. The objective of this study is to assess the impact of AR and VR technology on knowledge acquisition, performance, user acceptance, and motivation. This was achieved through a comparative analysis of AR and VR mobile applications in a learning environment for chemistry experiments. The evaluation involved three main phases: pre-test, post-test and exchange phase. A total of 32 participants were recruited for the between-subject evaluation. Each group completed demographic forms and knowledge tests to ensure balanced representation. Afterwards, the participants were required to complete the knowledge test and questionnaire in the post-test. While in the exchange phase, it was held to acquire participants’ preferences on the best application to conduct chemistry experiments. The results reveal significant findings for both groups, indicating that AR and VR applications offer enhanced learning experiences. The results showed significant improvements in knowledge acquisition for both AR and VR groups, with both AR and VR groups demonstrating a substantial increase in knowledge scores in the post-test phase. Notably, the AR score was 44

In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC50 values of 3.8 and 7.8 μg/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8-epi-acuminolide (1) and foetidalabdane A (4), and three known labdane diterpenoids, acuminolide (2), 17-O-acetylacuminolide (3), and spiroacuminolide (5). A new norlabdane diterpene, 16-foetinorlabdoic acid (6), was also isolated and identified. Excluding compounds 5 and 6, all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC50 values of 63.3 and 93.5 μM, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1, 2, and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC50 values of 76.0, 31.9, and 14.9 μM, respectively.

The phytochemical investigation on Mesua lepidota T. Anderson led to the identification of eight Mammea coumarins [lepidotols A-B (1–2), lepidotol E (3), lepidotins A-C (4–6), mammea A/BB cyclo F (7), and ochrocarpin E (8)], five triterpenes [friedelin (9), friedelinol (10), betulinic acid (11), glutinol (12), and α-amyrin (13)], one xanthone, namely pyranojacareubin (14), and two sterols [β-sitosterol (15) and stigmasterol (16)]. Identification was conducted by 13C-NMR dereplication and after a conventional isolation process. The structural elucidation of the isolated compounds was conducted through the analysis of spectroscopic data and comparison with literature data. The chemotaxonomic significance of all compounds was discussed, highlighting that most compounds were isolated only in the Mesua genus, or specifically from Mesua lepidota. In addition, glutinol (12) was isolated for the first time from the genus Mesua.

The Zingiber zerumbet rhizomes are traditionally used to treat fever, and the in vitro inhibitory effect of ethyl acetate extract from Zingiber zerumbet rhizomes (EAEZZR) against DENV2 NS2B/NS3 (two non-structural proteins, NS2 and NS3 of dengue virus type 2) has been reported earlier. This study was carried out to establish an acute toxicity profile and evaluate the anti-fever (anti-pyretic) activities of EAEZZR in yeast-induced fever in rats. The major compound of EAEZZR, zerumbone, was isolated using chromatographic methods including column chromatography (CC) and preparative thin-layer chromatography (PTLC). Additionally, the structure of zerumbone was elucidated using nuclear magnetic resonance (NMR), liquid chromatography mass spectrometer-ion trap-time of flight (LCMS-IT-TOF), infrared (IR), and ultraviolet (UV) spectroscopy. The toxicity of EAEZZR was evaluated using Organization for Economic Cooperation and Development Test Guideline 425 (OECD tg-425) with minor modifications at concentrations EAEZZR of 2000 mg/kg, 3000 mg/kg, and 5000 mg/kg. Anti-fever effect was determined by yeast-induced fever (pyrexia) in rats. The acute toxicity study showed that EAEZZR is safe at the highest 5000 mg/kg body weight dose in Sprague Dawley rats. Rats treated with EAEZZR at doses of 125, 250, and 500 mg/kg exhibited a significant reduction in rectal temperature (TR) in the first 1 h. EAEZZR at the lower dose of 125 mg/kg showed substantial potency against yeast-induced fever for up to 2 h compared to 0 h in controls. A significant reduction of TR was observed in rats treated with standard drug aspirin in the third through fourth hours. Based on the present findings, ethyl acetate extract of Zingiber zerumbet rhizomes could be considered safe up to the dose of 5000 mg/kg, and the identification of active ingredients of Zingiber zerumbet rhizomes may allow their use in the treatment of fever with dengue virus infection.

The phytochemical studies on the bark of Cyathostemma wrayi King resulted in the identification of ten alkaloids consisting of four oxoaporphines; lysicamine (1), atherospermidine (2), thalicminine (3), liriodenine (4), five aporphines; xylopine (5), nornuciferine (6), annonaine (7), norstephalagine (8), asimilobine (9), and one propaporphine; stepharine (10). The structural characterisation of all the isolated alkaloids was confirmed through the analysis of spectroscopic data and comparison with literature data. This is the first report on the alkaloids of Cyathostemma wrayi and also the first report on the occurrence of aporphine (1-3) and proaporphine (5-10) alkaloids in the genus of Cyathostemma. In addition, the chemophenetic significance of the isolated alkaloids was summarized.

This study investigated the butyrylcholinesterase (BChE) inhibitory activity of harmane (1), naucledine (2), and dihydrodeglycocadambine (3) isolated from fractions F7 and F9 of Ochreinauclea maingayi. Both fractions demonstrated significant inhibition, exceeding 80%, against BChE at 100 µg/mL. Compound 2, is the most potent inhibitor, exhibiting an IC50 value of 22.08 µM, followed by 1 and 3 (IC50 23.96 and 30.32 µM, respectively). Docking studies revealed that 1 and 2 effectively bind to BChE, with binding energies of -51.24 and -57.17 kcal/mol, respectively. Kinetic analysis of 2 indicated mixed-mode inhibition of BChE, with a Ki of 6.08 μM. In the paralysis assay, 1 showed a weak delay in paralysis and reduced the paralysis ratio from 72.59 ± 4.7% to 60.00 ± 7.0% (12.59% reduction) followed by 2 with 70.00 ± 1.7% (2.59% reduction) compared with negative standard (DMSO 0.1%) on human amyloid β-protein in a transgenic Caenorhabditis elegans (CL4176) model.

Traditionally, Murraya koenigii (L.) Spreng has been used as an ingredient in medicinal formulations. Several studies have reported on the potential of M. koenigii leaves to enhance learning and memory functions in animal models. This study aimed to identify the chemical constituents and evaluate the anti-cholinesterase activity of the essential oil extracted from M. koenigii leaves. The essential oil extracted via hydrodistillation was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of 41 constituents were identified, with beta-phellandrene (35.42%), beta-caryophyllene (16.79%) and alpha-pinene (17.75%) predominating in the essential oil. Using Ellman's colorimetric method, the M. koenigii essential oil demonstrated potent inhibitory activity against acetylcholinesterase (AChE), with an IC50 value of 36.89 mu g/mL. Interestingly, a mixture of the three major constituents (beta-phellandrene, beta-caryophyllene, and alpha-pinene) was more effective than the individual constituents (beta-caryophyllene and alpha-pinene). In conclusion, the study on the neuroprotective effects of M. koenigii essential oil has yielded promising results.

The analysis of the constituents of the leaves of Tradescantia spathacea yielded one new phenolic compound, named 3,6-di-tert-butyl-5-ethylphenol (1), along with four known compounds consisting of 1,1′-oxybis(2,4-di-tert-butylbenzene), β-sitosterol, β-sitosterone, and stigmasterol. All the structures were depicted using different spectroscopic methods such as NMR, IR, UV, and MS. Compounds 2–5 were reported for the first time to be isolated from T. spathacea leaves. The antioxidant activities of the compounds were tested using a DPPH free radical scavenging assay. Compound 1 showed potent antioxidant activities, while other compounds showed no significant antioxidant properties.

Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrugresistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 +/- 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 +/- 3.37 mu M against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 mu M. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.

A total of thirteen compounds consisting of nine xanthones; cowagarcinone C (1), doitunggarcinone C (2), nigrolineaxanthone E (3), nigrolineaxanthone Q (4), beta-mangostin (5), 7-O-methylgarcinone E (6), dulcisxanthone F (7), ananixanthone (8) and nigrolineaxanthone N (9), two polycyclic polyprenylated acylphloroglucinols (PPAPs); garcinielliptone J (13) and garcinialone (14) as well as two terpenoids; 30-hydroxycycloartenol (15) and garcinane (16), were putatively identified with a good confidence level from dichloromethane extract of Garcinia griffithii T. Anderson using the 13C NMR-based dereplication and MixONat software. In addition, three xanthones; euxanthone (1,7-dihydroxyxanthone) (10), forbexanthone (11) and 1,5-hydroxy-3,6-dimethoxy-2,7diprenylxanthone (12) were successfully isolated. The structure of the isolated compounds was confirmed through the analysis of spectroscopic data and comparison with reported data. The 13C NMR data of forbexanthone (11) was reported for the first time. Interestingly, the dichloromethane extract and 1,5-dihydroxy3,6-dimethoxy-2,7-diprenylxanthone (12) which were evaluated for their exhibited alpha-glucosidase inhibitory activity exhibited potent inhibition toward the enzyme with IC50 values of 0.66 mu g/mL and 3.02 mu M, respectively as compared to the standard, acarbose (IC50 = 392 mu g/mL or 608 mu M). Notably, ananixanthone (8) has not been reported from the genus Garcinia while compounds 1-7, 9, 11 and 13-16 being reported from Garcinia griffithii for the first time. In addition, the chemophenetic significance of all the compounds has also been discussed.

Phytochemical investigation on the bark of Nauclea officinalis led to the isolation of a new monoterpenoid indole alkaloid, nauclediol. The structure of the compound was identified through extensive spectroscopic analysis. Nauclediol displayed cholinesterase-inhibitory activities towards AChE and BChE with IC50 values of 15.429 and 8.756 µM, respectively. Statistical analysis revealed that the mode of inhibition of nauclediol was non-competitive inhibitor for both AChE and BChE. Molecular docking revealed that nauclediol interacts with the choline-binding site and the catalytic triad of TcAChE and hBChE. This study also demonstrated the neuroprotective potential of nauclediol against amyloid beta-induced cytotoxicity and LPS-induced neuroinflammation activity in a dose-dependent manner.

Urea derivatives are an important class of pharmacologically-active compounds due to their ability to form hydrogen bonds with biological targets. Several synthetic pathways have been developed to access urea derivatives, such as the metal-free and metal-catalysed carbonylation reactions of amines and the Curtius, Hofmann, and Tiemann rearrangement reactions. This study aimed to synthesize urea derivatives from primary amines. The urea derivatives were synthesized from primary amines and potassium cyanate in 1M HCl aqueous solution under ambient conditions and were isolated, followed by characterization using FTIR, DSC, and NMR (H-1 and C-13). A new urea derivative, N, N-diethylaminopropylurea (6), together with N-phenylurea (1), para-tolylurea (2), ortho-methoxyphenylurea (3), para-methoxyphenylurea (4), N-benzylurea (5), and N-butylurea (7), was successfully synthesized under acidic conditions. This work presents the synthesis and characterization data of a newly-reported urea derivative, N, N-diethylaminopropylurea (6), and extends the substrate scope to basic side chains in the synthesis of urea derivatives from primary amines and potassium cyanate in water.

Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer’s disease (AD) drugs. The genus Alseodaphne, comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of A. pendulifolia Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, N-methyl costaricine (1), together with costaricine (2), hernagine (3), N-methyl hernagine (4), corydine (5), and oxohernagine (6). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds 1 and 2 were more-potent BChE inhibitors than galantamine with IC50 values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver–Burk plots of compounds 1 and 2 indicated they were mixed-mode inhibitors. Compounds 1 and 2 have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.