Significant Inhibitory Activity Research Articles

Pyridylpiperazine-based carbodithioates as urease inhibitors: synthesis and biological evaluation

The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives 5a–5n and 7a–7n that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives 5a–5n and 7a–7n were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography–mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, 5j (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC50 value of 5.16 ± 2.68 μM. This IC50 value is notably lower than that of thiourea (23 ± 0.03 μM), indicating the significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified.

Structural modification of 2-phenylquinoline-4-carboxylic acid containing SIRT3 inhibitors for the cancer differentiation therapy.

Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound P6. A total of 33 compounds were designed and synthesized. In the enzyme inhibitory assay, several molecules S18, S26, S27 and T5 showed potent SIRT3 inhibitory activity with IC50 value of 0.53, 1.86, 5.06, and 2.88 μM, respectively. Moreover, the tested compounds exhibited SIRT3 inhibitory selectivity over SIRT1 and SIRT2. Compounds S27 and T5 were potent in inhibition the growth of MM1.S and RPMI-8226 cells in the invitro antiproliferative test. Significantly, representative compounds, especially S27 and T5, promoted differentiation of tested MM cells in the cellular morphological evaluation, accompanied by increasing the expression of differentiation antigen CD49e and human immunoglobulin light chain lambda and kappa. Additionally, molecule S18 without antiproliferative potency itself, showed significant inhibitory activity against growth factor IL-6 induced RPMI-8226 cell proliferation. Collectively, potent SIRT3 selective inhibitors with MM cell differentiation potency were developed for further discovery of anticancer drugs.

Alginate Beads with Encapsulated Bioactive Substances from Mangifera indica Peels as Promising Peroral Delivery Systems

Since various bioactive substances are unstable and can degrade in the gastrointestinal tract, their stabilization is crucial. This study aimed to encapsulate mango peel extract (MPE) into edible alginate beads using the ionotropic gelation method for the potential oral delivery of bioactive substances. Mango peels, generally discarded and environmentally harmful, are rich in health-promoting bioactive substances. The alginate beads were examined for entrapment efficiency, particle size, morphology, thermal stability, physiochemical interactions, release profile under gastrointestinal conditions, and antibacterial efficacy. The study demonstrated the successful encapsulation of MPE with an efficiency of 63.1%. The in vitro release study showed the stability of the alginate beads in simulated gastric fluid with a maximum release of 45.0%, and sustained, almost complete release (99.4%) in simulated intestinal fluid, indicating successful absorption into the human body. In both fluids, the MPE release followed first-order kinetics. Encapsulation successfully maintained the antibacterial properties of MPE, with significant inhibitory activity against pathogenic intestinal bacteria. This is the first study on MPE encapsulation in alginate beads, presenting a promising oral delivery system for high-added-value applications in the food industry for dietary supplements, functional foods, or food additives. Their production is sustainable and economical, utilizing waste material and reducing environmental pollution.

Subcritical Water Extraction of Undaria pinnatifida: Comparative Study of the Chemical Properties and Biological Activities across Different Parts

The subcritical water extraction of Undaria pinnatifida (blade, sporophyll, and root) was evaluated to determine its chemical properties and biological activities. The extraction was conducted at 180 °C and 3 MPa. Root extracts exhibited the highest phenolic content (43.32 ± 0.19 mg phloroglucinol/g) and flavonoid content (31.54 ± 1.63 mg quercetin/g). Sporophyll extracts had the highest total sugar, reducing sugar, and protein content, with 97.35 ± 4.23 mg glucose/g, 56.44 ± 3.10 mg glucose/g, and 84.93 ± 2.82 mg bovine serum albumin (BSA)/g, respectively. The sporophyll contained the highest fucose (41.99%) and mannose (10.37%), whereas the blade had the highest galactose (48.57%) and glucose (17.27%) content. Sporophyll had the highest sulfate content (7.76%). Key compounds included sorbitol, glycerol, L-fucose, and palmitic acid. Root extracts contained the highest antioxidant activity, with IC50 values of 1.51 mg/mL (DPPH), 3.31 mg/mL (ABTS+), and 2.23 mg/mL (FRAP). The root extract exhibited significant α-glucosidase inhibitory activity with an IC50 of 5.07 mg/mL, indicating strong antidiabetic potential. The blade extract showed notable antihypertensive activity with an IC50 of 0.62 mg/mL. Hence, subcritical water extraction to obtain bioactive compounds from U. pinnatifida, supporting their use in functional foods, cosmetics, and pharmaceuticals is highlighted. This study uniquely demonstrates the variation in bioactive compound composition and bioactivities across different parts of U. pinnatifida, providing deeper insights. Significant correlations between chemical properties and biological activities emphasize the use of U. pinnatifida extracts for chronic conditions.

Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC50 1.0–9.0 μM in the tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition test. Lupane derivatives – 1-oxime 7, 1,10-seco-hydroxynitrile 11 and furanoterpenoid 14 – were selected as those expected to be the most promising compounds. The results of molecular modeling evinced the strongest binding of compound 11 to the active site of Tdp1 compared to the reference drug. Simultaneously, only compound 11 at subtoxic concentration (10 μM) produced a synergetic effect on the topotecan activity against HeLa-V cells.

Synthesis and antitumor activity of new flavonoid hybrid peptidomimetics

To discover new antitumor drugs based on the structure of natural products, two series of d-2-Phenylglycine/D-Leucine hybridized isoflavone derivatives were synthesized, and their anti-proliferation activities against human cancer cells were evaluated in vitro. Most target compounds exhibit potent anti-proliferative activity against HeLa cells, among which the inhibitory ability of compound 8 s is close to the positive control. Compound 8 s showed significant broad-spectrum inhibitory activity against cancer cells (HeLa, MCF-7, MDA-MB231, and H460 cells) with IC50 values of 1.94±0.26 µM, 4.75±0.38 µM, 8.56±0.19 µM, and 4.36±0.11 µM, respectively. Furthermore, compound 8 s was discovered to have certain inhibitory effects on HeLa cell proliferation, apoptosis, invasion, and migration. Molecular docking experiments and in vitro enzyme inhibition assays revealed that 8 s binds to APN and inhibits its enzyme activity, which is likely a key factor contributing to its antitumor effects. Altogether, this study proposes compound 8 s as a new lead with great promise for further antitumor research.

Undobolins A-L, Ophiobolin-Type Sesterterpenoids from Aspergillus undulatus.

Twelve previously undescribed ophiobolin-type sesterterpenoids, undobolins A-L (1-12), were isolated from Aspergillus undulatus, and their structures were elucidated by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction experiments. Compound 1 was the second example of 20-nor-ophiobolin reported, while compounds 2-6 were notable for oxygenation of C-2, and compound 6 showed significant inhibitory activity against ConA-induced T lymphocyte proliferation with an IC50 value of 2.3 μM, which suggests a promising new direction in the quest for immunosuppressive agents.

LC–ESI–MS/MS-based molecular networking, antioxidant, anti-glioma activity and molecular docking studies of Clematis graveolens

Clematis graveolens Lindl., an indigenous climbing plant found in the Himalayan areas, is used by local communities for the treatment of neck tumors. The objective of this work is to examine the comprehensive metabolomic profile, antioxidant capability, in vitro and in silico anti-glioma effects on U-87 human glioma cell lines of the crude extract and fractions from C. graveolens. Liquid chromatography coupled with mass spectroscopy (LC–MS/MS) was used to establish detailed metabolite profiling of C. graveolens. The assessment of cell cytotoxicity was conducted using MTT cell viability assay on U-87 and BHK-21. Through molecular docking studies, the mode of inhibition and binding interaction between identified compounds and target proteins were also determined to evaluate the in vitro results. The use of LC–MS/MS-based global natural products social (GNPS) molecular networking analysis resulted in the identification of 27 compounds. The crude extract, ethyl acetate fraction, and chloroform fraction exhibited significant inhibitory activity against the U-87 cell lines, with IC50 values of 112.0, 138.1, and 142.7 µg/mL, respectively. The ethyl acetate fraction exhibited significant inhibitory concentration for 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity and the metal chelation activity with IC50 value of 39.50 µg/mL, 32.27 µg/mL, and 53.46 µg/mL, respectively. The crude extract showed maximum total phenolic, and total flavonoid concentration measuring 338.7 µg GAE/mg, and 177.04 µg QE/mg, respectively. The findings of this study indicate that C. graveolens consists of a diverse range of active phytoconstituents that possess antioxidant and anti-glioma properties.

Structure, anti-inflammatory and anti-bacterial activities of novel pentacyclic triterpenoids and other constituents from the leaves of Pittosporum elevaticostatum

The investigation of the leaves of Pittosporum elevaticostatum Chang et Yan led to the isolation of fifteen pentacyclic triterpenoids (1–15), including five previously undescribed ones (1–5), and nine others (16–24). The structures of compounds 1–5 were elucidated based on comprehensive spectroscopic techniques, including one dimension (1D) and 2D nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HR-ESI-MS), and other methods. Compounds 2 and 13 demonstrated significant inhibitory activity against Listeria monocytogenes (L. monocytogenes) with minimum inhibitory concentration (MIC) values of 32 μM. Scanning electron microscopy (SEM) observations revealed insights into the antibacterial mechanism, indicating that compounds 2 and 13 either prevent biofilm formation of dispersed the preformed cell membranes. Additionally, compounds 1, 5, 7, and 12 exhibited anti-inflammatory activity on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells with IC50 values ranging from 11.27 to 17.80 μM.

Design, Synthesis, and Evaluation of New Pyrazolines As Small Molecule Inhibitors of Acetylcholinesterase.

In pursuit of identifying small molecule inhibitors of acetylcholinesterase (AChE), the synthesis of new 2-pyrazolines was performed efficiently. A modified spectrophotometric method was used to examine their inhibitory effects on AChE as well as butyrylcholinesterase. Four compounds (2a, 2g, 2j, and 2l) were identified as selective AChE inhibitors. Molecular docking studies were conducted to explore their potential interactions with the active site of AChE (PDB code: 4EY7). 1-(3-Nitrophenyl)-3-(thiophen-3-yl)-5-[4-(4-morpholinyl)phenyl]-2-pyrazoline (2l) exerted significant AChE inhibitory action with an IC50 value of 0.040 μM close to donepezil (IC50 = 0.021 μM). In addition to π-π interactions with Tyr341, Tyr124, and Trp86 residues, compound 2l was also capable of forming two hydrogen bonds and a salt bridge at the active site of AChE thanks to its nitro group at the meta position of the phenyl moiety linked to the N 1 position of the pyrazoline scaffold. The higher inhibitory effect of compound 2l on AChE when compared to other compounds in this series might be explained by these additional interactions. Based on the in vitro parallel artificial membrane permeability assay, compound 2l was found to have high blood-brain barrier permeability. In vitro and in silico studies suggest that compound 2l is a potent inhibitor of AChE, which is an important target for neurodegenerative disorders, particularly Alzheimer's disease.

Formulation of 1% α-mangostin in orabase gel induces apoptosis in oral squamous cell carcinoma

BackgroundPlant-derived compounds have chemopreventive properties to be used as alternative medicine. Pericarp of Mangosteen (Garcinia mangostana Linn.), a tropical fruit in Southeast Asia contains a phytochemical α-mangostin (α-MG) that demonstrates potent anticancer effects against various types of cancer. α-MG has been reported to be the most effective agent in human cancer cell lines. The objectives of this study were to develop oral gel formulations containing α-MG and determine their (1) anticancer activity, (2) anti-HPV-16 and antimicrobial activities, (3) nitric oxide (NO) inhibitory activity, and (4) wound healing effect.MethodsFormulations of oral gel containing α-MG were developed. Anticancer activity on SCC-25 was assessed. Apoptotic induction was determined using flow cytometry technique. Antiviral activity against HPV-16 pseudovirus and antimicrobial activity against S. mutans, P. gingivalis and C. albicans were investigated. NO inhibition was carried out. Fibroblast cell migration was determined by in vitro scratch assay.ResultsThe formulation of 1% α-MG in orabase gel demonstrated anticancer activity by promoting apoptosis in SCC-25. The induction of apoptotic activity was dose dependent with pronounced effect in late apoptosis. The formulation appeared to reduce cell viability of oral keratinocytes (OKC). At CC50 it showed an inhibition against HPV-16 pseudovirus infection. The formulation had no antimicrobial activity against S. mutans, P. gingivalis and C. albicans. No significant NO inhibitory activity and wound healing effects were found.Conclusions1% α-MG in orabase gel exhibited anticancer activity by inducing apoptosis although low level of cytotoxicity observed in OKC was present. The appropriate carrier for novel nano-particles targeting cancer cells should be further investigated.

Benzothiazole‐Piperazine Hybrids Effectively Target C4‐2 Castration‐Resistant Prostate Cancer Cells in vitro Implicated through Computational Studies

AbstractA series of new analogs based on benzothiazole‐piperazine conjugates were synthesized and assessed to investigate their anticancer properties using in vitro and in silico techniques. The compounds 3 a–3 h were tested against prostate (C4‐2) cancer cells, and the results revealed that all the compounds showed significant inhibitory activity against C4‐2 cells (>50 % inhibition at 20 μM). Among all, 2‐(4‐(pyrimidin‐2‐yl) piperazin‐1‐yl) benzo[d]thiazole demonstrated the most prominent activity in the cell viability assay conducted displaying an IC50 value of 19.98 μM. In vitro studies have demonstrated that the compound can selectively target the androgen receptor (AR) and reduce the expression of several androgen‐responsive genes, including EAF2, ELL2, PSA and CALR genes, in castration‐resistant prostate cancer cells. Molecular docking results also revealed that all the compounds exhibited good energy binding scores against the androgen receptor target (PB ID: 2PNU) particularly compound 3 g which showed a maximum binding energy of −9.87 kcal/mol followed by other compounds as well as the established prostate cancer drug, enzalutamide, with a binding energy of −5.66 kcal/mol. Docking results were further supported by MD simulation studies, which confirmed that the ligand+protein complex was in stable conformation throughout the simulation time of 100 nanoseconds. Collectively, the present results, stemming from a combination of in vitro and in silico examinations, demonstrate that compound 3 g displays notable anti‐cancer characteristics, implying its viability as a prospective anti‐cancer pharmaceutical subject to clinical validation and subsequent development.

NMR-Guided Isolation of Anti-inflammatory Carabranolides from the Fruits of Carpesium abrotanoides L.

Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1-11), along with five known ones (12-16), were isolated from the fruits of Carpesium abrotanoides L. Compounds 1-11 are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2-4, 15, and 16 exhibited significant inhibitory activity against LPS-induced NO release with an IC50 value of 5.6-9.1 μM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.

Synthesis and Biological Evaluation of Novel 2-Aroyl Benzofuran-Based Hydroxamic Acids as Antimicrotubule Agents.

Because of synergism between tubulin and HDAC inhibitors, we used the pharmacophore fusion strategy to generate potential tubulin-HDAC dual inhibitors. Drug design was based on the introduction of a N-hydroxyacrylamide or a N-hydroxypropiolamide at the 5-position of the 2-aroylbenzo[b]furan skeleton, to produce compounds 6a-i and 11a-h, respectively. Among the synthesized compounds, derivatives 6a, 6c, 6e, 6g, 11a, and 11c showed excellent antiproliferative activity, with IC50 values at single- or double-digit nanomolar levels, against the A549, HT-29, and MCF-7 cells resistant towards the control compound combretastatin A-4 (CA-4). Compounds 11a and 6g were also 10-fold more active than CA-4 against the Hela cell line. When comparing the inhibition of tubulin polymerization versus the HDAC6 inhibitory activity, we found that 6a-g, 6i, 11a, 11c, and 11e, although very potent as inhibitors of tubulin assembly, did not have significant inhibitory activity against HDAC6.

Bioactive Phenylpropanoid Glycosides, Dimers, and Heterodimers from the Bark of Cinnamomum cassia (L.) J.Presl.

Six new phenylpropanoid glycosides (1-6), two new phenylethanol glycosides (7 and 8), one new phenylmethanol glycoside (9), three new phenylpropanoid dimers (10-12), two new phenylpropanoid-flavan-3-ol heterodimers (13 and 14), and six known relevant compounds (15-20) were isolated and identified from the well-liked edible and medicinal substance (the bark of Cinnamomum cassia (L.) J.Presl). The structures of these isolates were determined by using spectroscopic analyses, chemical methods, and quantum chemical calculations. Notably, compounds 4-9 were rare apiuronyl-containing glycosides, and compounds 13 and 14 were heterodimers of phenylpropanoids and flavan-3-ols linked through C-9″-C-8 bonds. The antioxidant and α-glucosidase inhibitory activities of all isolates were evaluated. Compounds 10 and 12 exhibited DPPH radical scavenging capacities with IC50 values of 20.1 and 13.0 μM, respectively (vitamin C IC50 value of 14.3 μM). In the ORAC experiment, all these compounds exhibited different levels of capacity for scavenging free radicals, and compound 10 displayed extraordinary free radical scavenging capacity with the ORAC value of 6.42 ± 0.01 μM TE/μM (EGCG ORAC value of 1.54 ± 0.02 μM TE/μM). Compound 12 also showed significant α-glucosidase inhibitory activity with an IC50 of 56.3 μM (acarbose IC50 of 519.4 μM).

Green Synthesis and Anticancer Activity of New Bis-Imidazole-Thiazole Hybrids Targeting Hepatocellular Carcinoma

Background: Given the inadequacies of current chemotherapy, there is a need for more effective anticancer agents. Imidazole and thiazole compounds have demonstrated significant biological activity, making them promising candidates. Aims and Objective: This study investigates the anticancer potential of imidazole and thiazole derivatives, focusing on liver cancer. The aim is to synthesize bis-imidazole-thiazole hybrids and evaluate their efficacy as anticancer agents against hepatocellular carcinoma. Methods: The hybrids were synthesized using (2,2'-((1,4-phenylenebis(2-mercapto-4-methyl1H-imidazole-1,5-diyl))bis(ethan-1-yl-1-ylidene))bis(hydrazine-1-carbothioamide), hydrazonoyl halides, and α-halo ketones, catalyzed by DABCO. This method is designed to be fast, yield high amounts of product, and be environmentally friendly. Structural confirmation was provided by FT IR, NMR, and MS spectroscopy. Results: The synthesized hybrids were tested in vitro against HepG-2 and WI-38 cell lines. Compounds 16b, 14a, 16a, and 7b showed significant inhibitory activity, with IC50 values indicating strong inhibition comparable to or better than the standard drug Sorafenib. Conclusion: The bis-imidazole-thiazole hybrids exhibit potent anticancer properties, particularly against hepatocellular carcinoma, making them potential candidates for future cancer therapies. Their selectivity and safety were further demonstrated by their effects on normal WI-38 human fibroblasts.

Phytochemistry, Anti-Tyrosinase, and Anti-Diabetes Studies of Extracts and Chemical Constituents of Dicerothamnus rhinocerotis Leaves

Dicerothamnus rhinocerotis (L.f.) Koekemoer, also known as rhinoceros bush and previously called Elytropappus rhinocerotis (L.f.) Less., is from the Asteraceae plant family. The plant is traditionally used to treat indigestion, stomach ulcers, influenza, and diarrhea. This study was aimed at investigating the phytochemistry, anti-glucosidase, anti-amylase, and anti-tyrosinase effects of D. rhinocerotis as research in this area is limited. The air-dried plant materials were macerated in 80% methanol (MeOH) and fractionated between hexane, dichloromethane (DCM), ethyl acetate (EtOAc), and butanol (BuOH). Column chromatography on silica gel was employed for the isolation of the compounds. A total of six compounds (1–6) were isolated from the fractions viz. acacetin (1), 15-hydroxy-cis-clerodan-3-ene-18-oic-acid (2), acacetin-7-glucoside (3), pinitol (4), apigenin (5), and β-sitosterol-3-O-glycoside (6). Compounds 2–4 and 6 are reported for the first time from this plant. Among the different fractions, the BuOH and EtOAc fractions had strong tyrosinase inhibitory activities with IC50 values of 13.7 ± 1.71 and 11.6 ± 2.68 µg/mL, respectively, while among the isolated compounds, apigenin (5) had the strongest inhibitory activity, with an IC50 of 14.58 µM, which competes favorably with Kojic acid (17.26 µM). The anti-glucosidase assay showed good activity in three of the fractions and compound 5, while the anti-amylase assays did not show significant inhibition activity.

Two new pinophol derivatives from endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal

An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 μmol·L~(-1).

Anticancer activity of Araguspongine C via inducing apoptosis, and inhibition of oxidative stress, inflammation, and EGFR-TK in human lung cancer cells: An in vitro and in vivo study.

The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor(EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the presentstudy intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells.In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1β, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.

Design, synthesis and biological Evaluation of novel chromones having 3,4-dihydropyrimidin-2(1H)-one core at C-8 in combination with triazoles: New α-glucosidase inhibitors and anti-bacterial agents

The Biginelli reaction synthesizes dihydropyrimidones through a multi-component reaction. A β-ketoester, aldehyde, and urea or thiourea react in the presence of an acid catalyst to form these dihydropyrimidones. 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids (9a-9l) were synthesized by multiple steps including one pot Biginelli multicomponent reaction depicted in the scheme. An efficient method for the Biginelli reaction of Chromone aldehyde, acetoacetate esters, and urea employed in the presence of ferric chloride is described. In the end, we have successfully synthesized twelve derivatives of 3,4-Dihydropyrimidin-2(1H)-One/Chromone/Triazole hybrids and subjected them to testing for Antibacterial activity and α-glucosidase inhibition activity. Among these derivatives, compound 9g (IC50 = 142.92 nmol) and 9e (144.49 nmol) exhibited significant inhibitory activity in comparison to the positive control acarbose (IC50 = 350.91 nmol). Compound 9g demonstrated the most significant suppression against Escherichia coli and Bacillus cereus, with zone diameters of 8.8 ± 1.35 mm and 9.1 ± 0.23 mm, respectively. Compound 9b displayed a clear area where bacterial growth was inhibited, measuring 7.5 ± 1.25 mm against Klebsiella pneumonia. Compound 9k exhibited a zone of inhibition measuring 8 ± 1.2 mm in radius against Staphylococcus epidermidis. The docking results for the synthesized compounds indicate that compound 9b exhibited the most favorable docking score of −10 kcal/mol, whereas compound 9a had the second-best docking score of −8.7 kcal/mol. Molecular docking was utilized to examine the interactions between the title compounds and α-glucosidase, in order to provide valuable insights. The data obtained revealed significant interactions that contribute to the inhibitory effects of the drugs against α-glucosidase. These compounds exhibit significant potential as attractive initial candidates for the development of new α-glucosidase inhibitors.