Chromones from the endophytic fungus Bipolaris eleusines.

Eight previously undescribed chromones eleusineketones A-H (1-8), as well as eight known compounds (9-16), were isolated from the endophytic fungus Bipolaris eleusines. These planar structures were created using an in-depth analysis of their spectral data, which included 1D, 2D, and HRESIMS data. Furthermore, the absolute configurations of compounds 1, 2, and 6 were determined by spectroscopic analysis and quantum chemical computational approaches, and compound 5 was determined by single-crystal X-ray diffraction analysis. The cytotoxic activity assay revealed that compounds 1 and 5 both inhibited MDA-MB-231 cells with IC50 values of 14.48 µM and 17.99 µM, respectively.

Pyrano[2,3-b]chromone derivatives as novel dual inhibitors of α-glucosidase and α-amylase: Design, synthesis, biological evaluation, and in silico studies.

Inhibition of α-glucosidase and α-amylase is an important target for treatment of type 2 diabetes. In this work, a novel series of pyrano[2,3-b]chromene derivatives 5a-m was designed based on potent α-glucosidase and α-amylase inhibitors and synthesized by simple chemical reactions. These compounds were evaluated against the latter enzymes. Most of the title compounds exhibited high inhibitory activity against α-glucosidase and α-amylase in comparison to standard inhibitor (acarbose). Representatively, the most potent compound, 4-methoxy derivative 5d, was 30.4 fold more potent than acarbose against α-glucosidase and 6.1 fold more potent than this drug against α-amylase. In silico molecular modeling demonstrated that compound 5d attached to the active sites of α-glucosidase and α-amylase with a favorable binding energies and established interactions with important amino acids. Dynamics of compound 5d also showed that this compound formed a stable complex with the α-glucosidase active site. In silicodrug-likeness as well as ADMET prediction of this compound was also performed and satisfactory results were obtained.

Two new 2-(2-phenylethyl)chromone derivatives and two sesquiterpenes from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Two new 2-(2-phenylethyl)chromones (1-2), two new sesquiterpenes (12-13), and twelve known compounds (3-11, 14-16) were isolated from agarwood of Aquilaria sinensis. These structures were confirmed by HRESIMS, 1D and 2D NMR spectra. The absolute configurations of two new sesquiterpenes were determined by comparing the experimental and calculated ECD spectra. Among them, 7,8-dihydroxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (2) was the first time found that the hydroxyl groups at both C-7/C-8 in agarwood. And Aseudesm B (13), the aldehyded methyl group at C-5 of eucalyptane sesquiterpenes was first discovered in natural products. In the bioassays, all compounds were evaluated for their inhibitory activity against lipopolysaccharide-activated nitric oxide (NO) production in RAW264.7 cells. Compounds 2-5, 7, 9-10, and 13-14 revealed notable inhibitory effects against NO production with IC50 values ranging from 4.0 to 13.0 µM.

A pair of new chromone enantiomers from Xylaria nigripes.

A pair of new chromone derivative enantiomers, (+)-xylarichromone A (1a) and (-)-xylarichromone A (1b), were isolated from the solid fermentation of Xylaria nigripes. The planar structure of 1 was determined by extensive NMR spectroscopic data, and its absolute configuration was assigned by comparison the ECD spectra with the known chromone derivatives. Compound 1 was the first chromone derivative reported from this medicinal fungus. The neuroprotective effects of 1 against oxygen and glucose deprivation (OGD) induced pheochromocytoma-12 cells (PC12) injury was investigated.

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases.

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

BACKGROUND: COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives' ability to inhibit viral entry and prevent replication. METHOD: This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa's rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. RESULT: The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of - 19.54 kcal/mol. CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

Enzymatic biosynthesis of novel 2-(2-phenylethyl)chromone glycosides catalyzed by UDP-glycosyltransferase UGT71BD1.

2-(2-Phenylethyl)chromones (PECs) are the main bioactive components of agarwood which showed diverse pharmaceutical activities. Glycosylation is a useful structural modification method to improve compounds' druggability. However, PEC glycosides were rarely reported in nature which largely limited their further medicinal investigations and applications. In this study, the enzymatic glycosylation of four naturally separated PECs 1-4 was achieved using a promiscuous glycosyltransferase UGT71BD1 identified from Cistanche tubulosa. It could accept UDP-Glucose, UDP-N-acetylglucosamine and UDP-xylose as sugar donors and conduct the corresponding O-glycosylation of 1-4 with high conversion efficiencies. Three O-glucosylated products 1a (5-hydroxy-2-(2-phenylethyl)chromone 8-O-ß-D-glucopyranoside), 2a (8-chloro-2-(2-phenylethyl)chromone 6-O-ß-D-glucopyranoside) and 3a (2-(2-phenylethyl)chromone 6-O-ß-D-glucopyranoside) were prepared and structurally elucidated as novel PEC glucosides based on NMR spectroscopic analyses. Subsequent pharmaceutical evaluation found that 1a showed remarkably improved cytotoxicity against HL-60 cells, whose cell inhibition rate was 19 times higher than that of its aglycon 1. The IC50 value of 1a was further determined to be 13.96 ± 1.10 µM, implying its potential as a promising antitumor-leading candidate. To improve the production of 1, docking, simulation and site-directed mutagenesis were performed. The important role of P15 in the glucosylation of PECs was discovered. Besides, a mutant K288A with a two-fold increased yield for 1a production was also afforded. This research reported the enzymatic glycosylation of PECs for the first time, and also provide an eco-friendly pathway for the alternative production of PEC glycosides for leading compounds discovery.

Selective Induction of DNA Damage and Cell Cycle Arrest Mediated by Chromone-Triazole Dyads Derivatives: Effects on Breast and Prostate Cancer Cells.

Chromones and triazoles are groups of heterocyclic compounds widely known to exhibit a broad spectrum of biological activities. The combination of these two pharmacophores could result in multiple mechanisms of action to increase the potency of anticancer drugs and reduce their side effects. The in vitro antitumor effect of eight chromone-based compounds was evaluated in breast (T-47D and MDA-MB-231) and prostate (PC3) cancer cell lines, and in non-cancerous human mammary epithelial cells (HuMEC) using a resazurin-based method. Flow cytometry was used to evaluate the cell cycle and cell death, and É£-H2AX detection to identify DNA damage. The compounds showed selective cytotoxicity against cancer cell lines, with (E)-2-(2-(5-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl)vinyl)-4H-chromen-4-one (compound 2 a) being more potent in non-metastatic T-47D cells (IC50 0.65 µM). Replacing the hydrogen by a methyl group on the triazole ring in compound 2 b enhanced the cytotoxic activity up to IC50 0.24 µM in PC3, 0.32 µM in MDA-MB-231 and 0.52 µM in T-47D. Compound 2 b was 3-fold more potent than doxorubicin in PC3 (IC50 0.73 µM) and 4-fold in MDA-MB-231 (IC50 1.51 µM). The addition of tetrahydroisoindole-1,3-dione moiety in compound 5 did not improve its effectiveness in any of the cell lines but it exerted the lowest cytotoxic effect in HuMEC (IC50 221.35 µM). The compounds revealed different cytotoxic mechanisms: 2 a and 2 b induced G2/M arrest, and compound 5 did not affect the cell cycle.

Eight new 2-(2-phenylethyl)chromone derivatives from agarwood of Aquilaria sinensis with anti-inflammatory activity.

Eight previously unknown 2-(2-phenylethyl)chromone derivatives, called aquichromones A - E (1-3, 5 and 6) and 8-epi-aquichromone C (4), including two pairs of enantiomers [(±)-1 and (±)-2] were isolated from the agarwood of Aquilaria sinensis. The structures and absolute stereochemistry of these natural products were elucidated by using spectroscopic and computational methods. The result of biological assay showed that two members of this group, 4 and 5, have significant dose-dependent anti-inflammatory activity.

Chemical constituents with senolytic activity from the stems of Limacia scandens.

While screening senotherapeutics from natural products, seven undescribed chemicals, two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, as well as six known compounds were isolated from the stems of Limacia scandens. The structures of compounds were elucidated through spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and CD data. All compounds were tested in replicative senescent human dermal fibroblasts (HDFs) to determine their potential as senotherapeutic agents to specifically target senescent cells. One tigliane and two chromones derivatives showed senolytic activity, indicating that senescent cells were selectively removed. Especially, 2-{2-[(3'-O-ß-d-glucopyranosyl)phenyl]ethyl}chromone is expected to be a potential senotherapeutics by inducing HDF death, inhibiting the activity of senescence-associated ß-galactosidase (SA-ß-gal) and expressing senescence-associated secretory phenotype (SASP) factors.

A new chromone from Kandelia candel endophytic fungus Aspergillus sp. ZJ-68.

One chromone (1), together with four known alkaloids, were isolated from the mangrove endophytic fungus Aspergillus sp. ZJ-68. Their structures were elucidated by a combination of HRESIMS and NMR spectroscopic analyses. Compound 1 showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 4.094 ± 0.8 µM, which was better than positive drug indomethacin (IC50=35.8 ± 0.5 µM).

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20).

BACKGROUND: Loss of PTEN function leads to increased PI3Kß signaling. AZD8186, a selective PI3Kß/δ inhibitor, has shown anti-tumor activity in PTEN-deficient preclinical models. Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed in advanced gastric cancer with PTEN loss. METHODS: In the phase Ib dose-escalation, subjects with advanced solid tumors received oral AZD8186 (60 mg or 120 mg; twice daily (BID); 5 days on/2 days off) plus intravenous paclitaxel (70 mg/m2 or 80 mg/m2; days 1, 8, and 15) every 4 weeks. In the phase II part, MRGC patients with PTEN loss or PTEN/PIK3CB gene abnormality were enrolled and received recommended phase II dose (RP2D) of AZD8186 plus paclitaxel. Primary endpoints were to determine maximum tolerated dose (MTD) and RP2D in phase Ib and 4-month progression-free survival (PFS) rate in phase II. RESULTS: In phase Ib, both MTD and RP2D were determined at paclitaxel 80 mg/m2 and AZD8186 120 mg BID. In phase II, 18 patients were enrolled [PTEN loss (n = 18) and PIK3CB mutation (n = 1)]. The 4-month PFS rate was 18.8% (3 of 16 evaluable patients) and further enrollment stopped due to futility. CONCLUSION: Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569.

Pauciflorins A-E, Unexpected Chromone-Monoterpene-Derived Meroterpenoids from Centrapalus pauciflorus.

Five unusual meroterpenoids based on new carbon skeletons, pauciflorins A-E (1-5), were isolated by multistep chromatographic separations of a methanol extract of the aerial parts of Centrapalus pauciflorus. Compounds 1-3 are derived by the connection of a 2-nor-chromone and a monoterpene unit, whereas 4 and 5 are dihydrochromone-monoterpene adducts with a rarely occurring orthoester functionality. The structures were solved using 1D and 2D NMR, HRESIMS, and single-crystal X-ray diffraction. Pauciflorins A-E were evaluated for antiproliferative activity against human gynecological cancer cell lines, but were inactive (IC50 < 10 µM) in each case.

Exploring chromone sulfonamides and sulfonylhydrazones as highly selective ectonucleotidase inhibitors: Synthesis, biological evaluation and in silico study.

Ectonucleotidases, a well-known superfamily of plasma membrane located metalloenzymes plays a central role in mediating the process of purinergic cell signaling. Major functions performed by these enzymes include the hydrolysis of extracellular nucleosides and nucleotides which are considered as important cell-signaling molecules. Any (patho)-physiologically induced disruption in this purinergic cell signaling leads to several disorders, hence these enzymes are important drug targets for therapeutic purposes. Among the major challenges faced in the design of inhibitors of ectonucleotidases, an important one is the lack of selective inhibitors. Access to highly selective inhibitors via a facile synthetic route will not only be beneficial therapeutically, but will also lead to an increase in our understanding of intricate interplay between members of ectonucleotidase enzymes in relation to their selective activation and/or inhibition in different cells and tissues. Herein we describe synthesis of highly selective inhibitors of human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), containing chromone sulfonamide and sulfonylhydrazone scaffolds. Compound 1c exhibited highest (and most selective) h-IAP inhibition activity (h-IAP IC50 = 0.51 ± 0.20 µM; h-TNAP = 36.5%) and compound 3k showed highest activity and selective inhibition against h-TNAP (h-TNAP IC50 = 1.41 ± 0.10 µM; h-IAP = 43.1%). These compounds were also evaluated against another member of ectonucleotidase family, that is rat and human ecto-5'-nucleotidase (r-e5'NT and h-e5'NT). Some of the compounds exhibited excellent inhibitory activity against ecto-5'-nucleotidase. Compound 2 g exhibited highest inhibition against h-e5'NT (IC50 = 0.18 ± 0.02 µM). To rationalize the interactions with the binding site, molecular docking studies were carried out.

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity.

Fifteen new chromones, sadivamones A-E (1-5), cimifugin monoacetate (6), sadivamones F-N (7-15), together with fifteen known chromones (16-30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12-13, 18, 20-22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

Molecular docking, QSAR, pharmacophore modeling, and dynamics studies of some chromone derivatives for the discovery of anti-breast cancer agents against hormone-dependent breast cancer.

In search of new anti-breast cancer agents, the present study envisaged the design and synthesis of a series of benzopyran-chalcones. All the synthesized compounds were assayed for their in-vitro anticancer activity against ER + MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines using SRB assay. The synthesized compounds were found active against ER + MCF-7 cell lines. Based on the in-vitro data, in-silico analysis was performed using hormone-dependent breast cancer targets such as hER-α and aromatase because the compounds showed activity against MCF-7 cells and none was active against MDA-MB-231. The in-silico results supported the in-vitro anticancer activity suggesting the affinity of compounds toward hormone-dependant breast cancer. Compounds 4A1 to 4A3 were found to be most cytotoxic to MCF-7 cells with IC50 values of 31.87, 22.95, and 20.34 µg/ml, respectively (Doxorubicin IC50: <10 µg/ml). In addition, they showed the interactions with the amino acid residues of a binding cavity of an hER-α. Furthermore, quantitative structure-activity relationship (QSAR) studies were performed to reveal the vital structural features required for anticancer activity against breast cancer. Molecular dynamic simulation studies of hER-α and 4A3 in comparison with the raloxifene complex ensure the appropriate refinement of compounds in the dynamic system. Additionally, a generated pharmacophore model explored the essential pharmacophoric features of the synthesized scaffolds with respect to clinically used drug molecules for optimal hormone-dependant anti-breast cancer activity.Communicated by Ramaswamy H. Sarma.

New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production.

A new isopropyl chromone (1) and a new flavanone glucoside (2) together with eleven known compounds (3-13) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one (1), 5,7-dihydroxyflavanone 7-O-ß-D-(6''-O-galloylglucopyranoside) (2), strobopinin (3), demethoxymatteucinol (4), pinocembrin-7-O-ß-D-glucopyranoside (5), (2S)-hydroxynaringenin-7-O-ß-D-glucopyranoside (6), afzelin (7), quercetin (8), kaplanin (9), endoperoxide G3 (10), grasshopper (11), vomifoliol (12), litseagermacrane (13) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1, 2, 5, 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC50 values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 µM, respectively, while the IC50 values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 µM, compared to that of the positive control, NG -monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 32.50±1.00 µM.

Retrospective Review of Chromane Analogues as Anti-protozoal Leads: A Decade's Worth of Evolution.

Tropical, vector-borne, and neglected diseases with a limited number of medication therapies include Leishmaniasis, Malaria, Chagas and Human African Trypanosomiasis (HAT). Chromones are a large class of heterocyclic compounds with significant applications. This heterocycle has long aroused the interest of scientists and the general public from biosynthetic and synthetic points of view owing to its interesting pharmacological activities. Chromones and their hybrids and isomeric forms proved to be an exciting scaffold to investigate these diseases. The in vitro activities of Chromone, Chromane, and a panel of other related benzopyran class compounds against Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, Trypanosoma cruzi, and numerous Leishmanial and Malarial species were investigated in our previous studies. The current article briefly describes the neglected diseases and the current treatment. This review aims to attempt to find better alternatives by scrutinizing natural and synthetic derivatives for which chromones and their analogues were discovered to be a new and highly effective scaffold for the treatment of neglected diseases, including compounds with dual activity or activity against multiple parasites. Additionally, the efficacy of other new scaffolds was also thoroughly examined. This article also discusses prospects for identifying more unique targets for the disease, focusing on flavonoids as drug molecules that are less cytotoxic and high antiprotozoal potential. It also emphasizes the changes that can be made while searching for potential therapies-comparing existing treatments against protozoal diseases and the advantages of the newer chromone analogues over them. Finally, the structure- activity relationship at each atom of the chromone has also been highlighted.

Design, synthesis, biological evaluation, and docking study of chromone-based phenylhydrazone and benzoylhydrazone derivatives as antidiabetic agents targeting α-glucosidase.

To develop novel α-glucosidase inhibitors, a series of chromone-based phenylhydrazone and benzoylhydrazone derivatives were designed, synthesized, and evaluated their inhibitory effects on α-glucosidase. The target compounds were characterized using 1H NMR, 13C NMR, and high-resolution mass spectra. Some of the compounds showed a varying degree of α-glucosidase inhibitory activity with IC50 values ranging from 6.59 ± 0.09 to 158.55 ± 0.87 µM. Among them, compound 5c (IC50 = 6.59 ± 0.09 µM) was the most potent inhibitor by comparison with positive control acarbose (IC50 = 685.11 ± 7.46 µM). Enzyme kinetic, fluorescence analysis, circular dichroism spectra, and molecular docking techniques were employed to explain the underlying molecular mechanisms of 5c inhibition on α-glucosidase. In vivo sucrose-loading test showed that 5c could suppress the rise of blood glucose levels after loading sucrose in normal Kunming mice. The cytotoxicity assay indicated that 5c exhibited low cytotoxicity.

A highly efficient metal-free selective 1,4-addition of difluoroenoxysilanes to chromones.

A highly efficient metal-free selective 1,4-addition reaction of difluoroenoxysilanes to chromones was developed using the low-cost and readily available HOTf as the catalyst, which is a facile and straightforward method to access valuable C2-difluoroalkylated chroman-4-one derivatives. Interestingly, the products could be readily converted to the difluorinated bioisostere of the natural product (S)-2,6-dimethylchroman-4-one and a difluorinated benzo-seven-membered heterocycle via the Schmidt rearrangement reaction. In addition, the in vitro anti-proliferative activities of these synthesized derivatives against human colon carcinoma cells (HCT116) revealed that compound 3g exhibited potent inhibitory effect on HCT116 cancer cells with an IC50 value of 6.37 µM, representing a novel lead compound for further structural optimization and biological evaluation.