Oxoaporphine Alkaloids Research Articles

Confocal image of three oxoaporphine alkaloids in cancer cell lines and their interaction with DNA by multispectroscopic and molecular docking techniques

Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV–vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.

Effects of the oxoaporphine alkaloid hernandonine on dengue virus. Evidence for its mechanisms of action

BackgroundDengue, caused by the dengue virus (Orthoflavivirus dengue, encompassing DENV types 1-4), is a member of the Flaviviridae family. The symptoms of dengue range from subclinical or mild manifestations to potentially fatal complications. The management of severe dengue is exceptionally challenging due to the absence of effective antiviral medications. In this context, natural products, whether in the form of pure compounds or standardized plant extracts, have emerged as a promising source for the development of novel antiviral therapeutics. Hernandonine, an oxoaporphine alkaloid found in Hernandia nymphaeifolia (C. Presl) Kubitzki. serves both as a metabolite and an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase. PurposeThis study investigated the ability of hernandonine to inhibit DENV infection and explored its potential mechanisms. Study designTo assess the in vitro anti-DENV activity, cells or induced pluripotent stem cell (iPSC)-derived cerebral organoids were exposed to hernandonine before or after infection with DENV. Along with hernandonine, the endocytosis modulators, genistein, wortmannin, Methyl-β-cyclodextrin (MβCD) and lovastatin, were used in the assays. MethodsThe DENV infectivity and virion production in cells or cerebral organoids treated with compounds were determined. Various methods, including cell and cerebral organoids imaging, protein and gene detection were conducted to explore their antiviral mechanisms. ResultsThe results revealed notable antiviral properties of hernandonine, particularly in inhibiting DENV during the early stages of infection. Mechanistic analysis demonstrated that, akin to genistein, wortmannin, methyl-β-cyclodextrin (MβCD), and lovastatin, hernandonine exerted an influence on cholesterol-rich lipid rafts. It also restrained the pseudopodial movement ability of cells, potentially through the downregulation of cytoskeleton and endocytosis regulatory genes or protein expression. Moreover, hernandonine's virucidal activity was demonstrated. Hernandonine's inhibition of DENV infection was further validated in a disease-relevant iPSC-derived cerebral organoids model, a novel DENV-2 infection system worthy of further application. ConclusionThis study evidenced the potential of hernandonine as a novel candidate in the fight against DENV infection.

Gouregine, an α-Gem-Dimethyltetradehydrocularine Alkaloid, and Other Aporphinoid Alkaloids from the Bark of Guatteria olivacea (Annonaceae) and Their In Vitro Cytotoxic Activities.

Guatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α-gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O-methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O-methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively.

In-silico investigation of oxoaporphine alkaloids of Xylopia aethiopica against SARS-COV-2 main protease

Background: The ongoing coronavirus pandemic poses a significant social, economic, and health threat worldwide. The situation is exacerbated further by vaccine hesitancy and the ongoing development of mutant strains that could lead to drug resistance. It is therefore critical to find new anti-viral chemotherapeutic agents to reduce or end the epidemic. This study aimed to investigate the antiprotease activity of the oxoaporphine alkaloids in Xylopia aethiopica. Methods: Computational techniques such as molecular docking were used to probe the oxoaporphine alkaloids in the plant for their ability to inhibit the main protease of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The docking score calculations which quantifies the predictive binding affinity of both ligand and target was carried out using Auto-Dock Vina software. Results: The results showed that oxoaporphine alkaloids had a better binding affinity than hydroxychloroquine sulfate (standard). Similarly, the values of the chemical descriptors obtained for these alkaloids revealed notable profiles, and these alkaloids also have good oral bioavailability according to rule of five. Conclusion: These findings imply that these plant-based alkaloids could be investigated further as prospective leads against SARS-CoV-2 main protease. Furthermore, structural-activity relationships on these compounds could be an effective way to mitigate the predicted side effects

One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, 4B displayed the most potent activity with an IC50 value of 0.5 μM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by −NO2 significantly enhanced the anticancer activity. Mechanism studies indicated that 4 and 4B induced cell cycle arrest at G2/M phase; in contrast, 4V induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds 4, 4B and 4V, suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound 4B effectively inhibited tumor growth in a mouse xenograft model bearing T-24.

Antioxidant and Antimicrobial Screening of Isolated Alkaloids from <i>Tinospora crispa</i>

The antioxidant capacity by DPPH radical scavenging and antimicrobial activity by disk diffusion and broth microdilution method of nine isolated alkaloids from T. crispa were evaluated. All isolated alkaloids had been divided into three groups which were aporphine alkaloids, N-formylannonaine (1), N-formylnornuciferine (2), magnoflorine (9), oxoaporphine alkaloids, lysicamine (3) and liriodenine (4); and protoberberine alkaloids, columbamine(6), dihydrodiscretamine (7) and 4,13-dihydroxy-2,8,9-trimethoxydibenzo [a,g]quinolizinium (8). Protoberberine alkaloids showed (IC50 > 500-800 μg/mL) radical scavenging activity while oxaporphine alkaloids inhibited the growth of the Gram-positive bacteria, Staphylococcus aureus (+) and Enterococcus faecalis (+).The antioxidant and antimicrobial properties of different compounds support documented traditional use of T. crispa in wound healing and treatment of rheumatic, diarrhoea, ulcers, itches and wounds. Results of the present biological activity investigation further points to the potential of this plant species as a good source of natural antioxidant and preservative in food industry.

Intervention of standardized ethanol leaf extract of Annickia polycarpa, (DC.) Setten and Maas ex I.M. Turner. (Annonaceae), in Plasmodium berghei infested mice produced anti-malaria action and normalized gross hematological indices

Ethnopharmacological relevanceMalaria is a global public health burden due to large number of annual infections and casualties caused by its hematological complications. The bark of Annickia polycarpa is an effective anti-malaria agent in African traditional medicine. However, there is no standardization parameters for A. polycarpa. The anti-malaria properties of its leaf are also not known. Aim of the studyTo standardize the ethanol leaf extract of A. polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane's test. Materials and methodsMalaria was induced by inoculating female ICR mice with 1.0 × 107P. berghei-infected RBCs in 0.2 mL (i.p.) of blood. Treatment was commenced 3 days later with APLE 50, 200, 400 mg/kg p.o., Quinine 30 mg/kg i.m. (Standard drug) or sterile water (Negative control) once daily per group for 4 successive days. Anti-malarial activity and gross malaria indices such as hyperparasitemia, mean change in body weight and mean survival time (MST) were determined for each group. Changes in white blood cells (WBCs), red blood cells (RBCs), platelets (PLT) counts, hemoglobin (HGB) concentration, hematocrit (HCT) and mean corpuscular volume (MCV) were also measured in the healthy mice before infection as baseline and on day 3 and 8 after inoculation using complete blood count. Standardization was achieved by UHPLC-MS chemical fingerprint analysis and quantitative phytochemical tests. ResultsAPLE, standardized to its total alkaloids, phenolics and saponin contents, produced significant (P < 0.05) dose-dependent clearance of mean hyperparasitemia of 22.78 ± 0.93% with the minimum parasitemia level of 2.01 ± 0.25% achieved at 400 mg/kg p.o. on day 8. Quinine 30 mg/kg i.m. achieved a minimum parasitemia level of 6.15 ± 0.92%. Moreover, APLE (50–400 mg/kg p.o.) evoked very significant anti-malaria activity of 89.22–95.50%. Anti-malaria activity of Quinine 30 mg/kg i.m. was 86.22%. APLE also inverse dose-dependently promotes weight gain with the effect being significant (P < 0.05) at 50 mg/kg p.o. Moreover, APLE dose-dependently increased the MST of malaria infested mice with 100% survival at 400 mg/kg p.o. Quinine 30 mg/kg i.m. also produce 100% survival rate but did not promote (P > 0.05) weight gain. Hematological studies revealed the development of leukocytopenia, erythrocytosis, microcytic anemia and thrombocytopenia in the malaria infected mice which were reverted with the treatment of APLE 50–400 mg/kg p.o. or Quinine 30 mg/kg i.m. but persisted in the negative control. The UHPLC-MS fingerprint analysis of APLE led to identification of one oxoaporphine and two aporphine alkaloids (1–3). Alkaloids 1 and 3 are being reported in this plant for the first time. ConclusionThese results indicate that APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.

Secondary Metabolites from Leaves of Polyalthia lateriflora and Their Antimicrobial Activity

The study aimed to isolate and identify the phytochemical components of Polyalthia lateriflora leaves and evaluate the antimicrobial activity. Six well-known compounds, including three triterpene lupeol (1) betulinic acid (2), β-Sitosterol-β-D-glucoside (3) and three oxoaporphine alkaloids O-methylmoschotaline (4), liriodenine (5) and atherosperminine (6). Structural elucidation of compounds were established through spectroscopic techniques such as 1D and 2D NMR (1H and 13C, DEPT, COSY, NOESY, HMBC, HMQC), IR and LC-MS. The isolated compounds and crude extracted were tested for their antibacterial potential against several microorganisms including P. aeruginosa, E. coli, s, S. aureus, B. subtilis and Saccharomyces cerevisiae and its showed significant inhibition toward the organisms species with different concentration range.

Interaction of dicentrinone, an antitrypanosomal aporphine alkaloid isolated from Ocotea puberula (Lauraceae), in cell membrane models at the air-water interface

In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 ± 1.7 μM), similar to the positive control benznidazole (IC50 of 18.7 ± 4.1 μM), reduced mammalian cytotoxicity (CC50 > 200 μM), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, submitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level.

Identification of Anti-Inflammatory Constituents from Vietnamese Piper hymenophyllum

A new oxoaporphine alkaloid, (−)-(6aR,7R)-N-acetylnorushinsunine (1) together with eight known compounds (2–9) had been isolated from the aerial part of Vietnamese Piper hymenophyllum Miq., Piperaceae. The chemical structures of 1–9 were established mainly by spectroscopic, spectrometric, and chiroptical spectra. Their anti-inflammatory activity was evaluated against lipopolysaccharides-induced nitric oxide production in RAW264.7 cells in vitro. Among them, compounds 2–4 showed significant inhibitory activities against the lipopolysaccharide-induced nitric oxide production in RAW264.7 cells with IC50 values of 7.2, 9.3, and 4.5 μM, respectively. In addition, compounds 2 and 4 suppressed both lipopolysaccharides-induced cyclooxygenase-2 and inducible nitric oxide synthase expressions. These results proposed that Piper hymenophyllum and its constituents may exert anti-inflammatory effects.

Bioactive aporphine alkaloids from the stems of Dasymaschalon rostratum

Three undescribed aporphine alkaloids dasymaroine A (1), 3-methoxyoxoputerine N-oxide (2), and dasymaroine B (3), along with nine known analogues (4–12) were isolated from the stems of Dasymaschalon rostratum Merr. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. Compound 1 is a rarely reported nitro aporphine alkaloid and its absolute configuration was defined based on negative specific rotation and single-crystal X-ray diffraction. Compound 2 represents the first example of oxoaporphine alkaloid N-oxide. All compounds were evaluated for their activities of six pathogenic bacteria, 1 exhibited significant inhibition against Escherichia coli and Saphylococcus aureus with MIC values of 1.2 and 2.5 μM, respectively. As well as compounds 1–5, 7, 10, 12 were evaluated for their anti-HIV activities with EC50 ranged from 1.93 to 9.70 μM.

The production of alkaloids in Annona cacans seedlings is affected by the application of GA4+7 + 6-Benzyladenine

The Annonaceae family presents alkaloids with ecological functions and pharmacological interest. This is the first study to evaluate if the application of plant growth regulators to seeds of this family alters the production of alkaloids over time from germination. This study was carried out in four sequential stages of Annona cacans Warm. development from the resumption of embryo during seed imbibition with the application of plant regulator GA4+7 + 6-Benzyladenine. The concentration of total alkaloids was quantified using the oxoaporphine alkaloid liriodenine as reference standard. In addition, the liriodenine concentration was measured and the profile evaluated by ultra-high-performance liquid chromatography (UHPLC). Results have shown that alkaloids are present in all phases and in all tissues, at higher concentrations in roots (up to 100 times). The proportion of total alkaloids and liriodenine was modified in response to the application of plant regulators. Roots doubled the content of alkaloids and liriodenine. In cotyledonary leaves, the amount of total alkaloids decreased; however, liriodenine remained unchanged. Our results have shown that the use of plant growth regulators based on gibberellins and cytokinins modified the production of alkaloids in tissues in a specific way.

Oxoaporphine alkaloids from the barks of Platymitra siamensis Craib (Annonaceae) and their cytotoxicity against MCF-7 cancer cell line

Oxoaporphine alkaloids from the barks of Platymitra siamensis Craib (Annonaceae) and their cytotoxicity against MCF-7 cancer cell line

A New Oxoaporphine Alkaloid from the Root of Dasymaschalon glaucum

The first phytochemical investigation of the root of Dasymaschalon glaucum led to the isolation of a new oxoaporphine alkaloid 1 together with seven known compounds, duguevalline (2), stigmalactam (3), enterocarpam III (4), desmosdumotin B (5), spiraeamide (6), kaempferol-3- O-glucopyranoside (7) and β-sitosterol (8). The chemical structures of all isolated compounds were established on the basis of their spectroscopic data. The cytotoxic and anti-HIV 1-RT activities of isolated compounds were also evaluated.

Novel total syntheses of oxoaporphine alkaloids enabled by mild Cu-catalyzed tandem oxidation/aromatization of 1-Bn-DHIQs.

Novel total syntheses of oxoaporphine alkaloids such as liriodenine, dicentrinone, cassameridine, lysicamine, oxoglaucine and O-methylmoschatoline were developed. The key step of these total syntheses is Cu-catalyzed conversion of 1-benzyl-3,4-dihydro-isoquinolines (1-Bn-DHIQs) to 1-benzoyl-isoquinolines (1-Bz-IQs) via tandem oxidation/aromatization. This novel Cu-catalyzed conversion has been studied in detail, and was successfully used for constructing the 1-Bz-IQ core.

Facile total synthesis of lysicamine and the anticancer activities of the RuII, RhIII, MnII and ZnII complexes of lysicamine.

Lysicamine is a natural oxoaporphine alkaloid, which isolated from traditional Chinese medicine (TCM) herbs and has been shown to possess cytotoxicity to hepatocarcinoma cell lines. Reports on its antitumor activity are scarce because lysicamine occurs in plants at a low content. In this work, we demonstrate a facile concise total synthesis of lysicamine from simple raw materials under mild reaction conditions, and the preparation of the Ru(II), Rh(III), Mn(II) and Zn(II) complexes 1–4 of lysicamine (LY). All the compounds were fully characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR, as well as single-crystal X-ray diffraction analysis. Compared with the free ligand LY, complexes 2 and 3 exhibited superior in vitro cytotoxicity against HepG2 and NCI-H460. Mechanistic studies indicated that 2 and 3 blocked the cell cycle in the S phase by decreasing of cyclins A2/B1/D1/E1, CDK 2/6, and PCNA levels and increasing levels of p21, p27, p53 and CDC25A proteins. In addition, 2 and 3 induced cell apoptosis via both the caspase-dependent mitochondrial pathway and the death receptor pathway. in vivo study showed that 2 inhibited HepG2 tumor growth at 1/3 maximum tolerated dose (MTD) and had a better safety profile than cisplatin.

Isoquinoline alkaloids isolated from three Guatteria species

The chemical investigation of the aerial parts of Guatteria ferruginea collected in the National Park of Serra dos Órgãos, Teresópolis, Brazil and of Guatteria latifolia and Guatteria sellowiana collected in the National Park of Itatiaia, Itatiaia, Brazil resulted in the isolation and identification of six isoquinoline alkaloids, two aporphine alkaloids 3-hydroxy-nornuciferine (1), nornuciferine (2) and four oxoaporphine alkaloids lysicamine (3), isomoschatoline (4), liriodenine (5) and O-methylmoschatoline (6). The isoquinoline alkaloids were found in the species G. ferruginea, G. latifolia and G. sellowiana for the first time and they support the taxonomic position within the genus Guatteria. Isoquinoline alkaloids (5–6) can be considered chemotaxonomic markers of the subfamily Annonoideae.

New Azafluorenone Derivative and Antibacterial Activities of Alphonsea cylindrica Barks

A phytochemical study of Alphonsea cylindrica King (unreported) has led to the isolation of six alkaloids. The compounds were identified as kinabaline (1; azafluorenone alkaloid), muniranine (2), O-methylmoschatoline (3; oxoaporphine alkaloid), lysicamine (4), atherospermidine (5) and N-methylouregidione (6; 4, 5-dioxoaporphine alkaloid). The structures of the isolated compounds were determined based on the spectroscopic techniques and by comparison with data reported in the literature. Alkaloid 2 was isolated as a new derivative of azafluorenone while alkaloids 1, 3 – 6 were isolated for the first time from Alphonsea species. In addition, alkaloid 3 and 4 showed inhibition zone against Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus cereus in disc diffusion test. The minimum inhibition concentration (MIC) values of lysicamine (4) against S. aureus, B. cereus and P. aeruginosa were found to be smaller than O-methylmoschatoline (3). Therefore, the reported antibacterial activity showed the potential of this plant as natural antibacterial agent and supported the documented traditional use of Alphonsea sp. in the treatment of diarrhea and fever.

Positive electrospray ionization ion trap mass spectrometry and ab initio computational studies of the multi-pathway fragmentation of oxoaporphine alkaloids

We report herein the first collision induced dissociation (CID) study with oxoaporphine alkaloids by electrospray ionization ion-trap mass spectrometry (ESI-IT-MS) associated with ab initio computational studies and isotope labeling experiments. Product ion spectra for a set of 11 oxoaporphine alkaloids were carefully analyzed to assign fragmentation patterns for this natural products class. All common possibilities for different arrangements of the peripheral groups, methylene dioxide bridge, methoxyl, and hydroxyl substituents, were discussed based on MS data and ab initio calculations. We observed that the most suitable protonation site generally occurs on the heterocyclic nitrogen instead of the carbonyl oxygen atom at C-7. In some special cases, a gas-phase proton transfer occurs for compounds bearing a hydroxyl group at C-3, as confirmed by isotope labeling experiments. Results point that the substitution pattern drives the dissociation behaviors of oxoaporphine alkaloids.

Spectroscopic investigation, vibrational assignments, HOMO-LUMO, NBO, MEP analysis and molecular docking studies of oxoaporphine alkaloid liriodenine

A combined experimental and theoretical DFT study of the structural, vibrational and electronic properties of liriodenine is presented using B3LYP function with 6-311G (2d, p) basis set. The theoretical geometry optimization data were compared with the X-ray data for a similar structure in the associated literature, showing similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap, mapped molecular Electrostatic Potential (MEP) surface calculation, first and second order hyperpolarizabilities were also performed with the same calculation level. Theoretical UV spectrum agreed well with the measured experimental data, with transitions assigned. The molecular electrostatic potential map shows opposite potentials regions that forms hydrogen bonds that stabilize the dimeric form, which were confirmed by the close values related to the CO bond stretching between the dimeric form and the experimental IR spectra (1654cm−1 for the experimental, 1700cm−1 for the dimer form). Calculated HOMO/LUMO gaps shows the excitation energy for Liriodenine, justifying its stability and kinetics reaction. Molecular docking studies with Candida albicans dihydrofolate reductase (DHFR) and Candida albicans secreted aspartic protease (SAP) showed binding free energies values of −8.5 and −8.3kcal/mol, suggesting good affinity between the liriodenine and the target macromolecules.