a549

Theophylline monohydrate (Quibron) appears to inhibit phosphodiesterase and prostaglandin production, regulate calcium flux and intracellular calcium distribution, and antagonize adenosine. Theophylline monohydrate is a natural alkaloid derivative of xanthine isolated from the plants Camellia sinensis and Coffea arabica. Physiologically, this agent relaxes the bronchial smooth muscle, produces vasodilation (except in cerebral vessels), stimulates the CNS, stimulates the cardiac muscle, induces diuresis, and increases gastric acid secretion; it may also suppress inflammation and improve contractility of the diaphragm.

Naphthol AS-E (nAS-E) is an the KIX-KID interaction and CREB-mediated gene transcription inhibitor.

Astragaloside IV (AS-IV), an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells. Astragaloside IV is a bioactive saponin first isolated from the dried plant roots of the genus Astragalus, which is used in traditional Chinese medicine.1 It dose-dependently inhibits human adenovirus type 3 (HAdV-3) in A549 cells (IC50 = 23 μM; LC50 = 865 μM).It inhibits replication of HAdV-3 and decreases HAdV-3-induced apoptosis. It has diverse protective effects for the cardiovascular, immune, digestive, and nervous systems. In particular, it reduces myocardial infarct size in dogs when administered prior to coronary ligation and reduces reperfusion arrhythmias in isolated rat hearts.

H1k is an eudistomin Y fluorescent derivative and lysosome-targeted antiproliferative agent that dose-dependently increases autophagy signalling and down-regulates the expression of cyclin-dependent kinase (CDK1) and cyclin B1.

CLEFMA has anti-proliferative activity. CLEFMA inhibits tumor growth associated with NF-κB-regulated anti-inflammatory and anti-metastatic effects.

HOIPIN-1 (JTP0819958) is a selective and potent inhibitor of linear ubiquitin chain assembly complex (LUBAC) (IC50 >2.8 μM).HOIPIN-1 inhibits LUBAC-mediated NF-kB activation.

OTS186935 FA is a protein methyltransferase SUV39H2 inhibitor.OTS186935 FA inhibits tumor growth in MDA-MB-231 breast cancer cells and A549 lung cancer cells.

MC2590 is a potent and selective histone deacetylase (HDAC) inhibitor that inhibits HDAC1-3, -6, -8, and -10 activities, induces cell cycle arrest, and promotes apoptosis.

AMPK activator 2 hydrochloride is a fluoroguanidine-containing derivative that up-regulates the AMPK signaling pathway and down-regulates mTOR/4EBP1/p70S6K.AMPK activator 2 hydrochloride inhibits the proliferation and migration of human cancer cell lines (UMUC3, T24, A549).

ULK1-IN-2 is a potent ULK1 inhibitor with potential anticancer activity, inducing apoptosis while blocking autophagy.ULK1-IN-2 has high cytotoxicity against cancer cells, with an IC50 value of 1.94 μM against A549 cells.ULK1-IN-2 can be used for the study of non-small-cell lung cancer.

OTUB1/USP8-IN-1 is a potent OTUB1/USP8 inhibitor with potential anticancer activity, with IC50 values of 0.17 and 0.28 nM for OTUB1 and USP8, respectively.OTUB1/USP8-IN-1 can be used in the study of non-small-cell lung cancer.

iFSP1, a potent, selective, and glutathione-independent ferroptosis suppressor protein 1 (FSP1) (AIFM2) inhibitor with an EC50 of 103 nM, sensitizes diverse human cancer cell lines to ferroptosis inducers like (1S,3R)-RSL3. It uniquely triggers ferroptosis in GPX4-knockout cells overexpressing FSP1.

NAE-IN-M22 (NEDD8 inhibitor M22) is a selective, potent and reversible inhibitor of NEDD8 activating enzyme (NAE). NAE-IN-M22 inhibits multiple cancer cell lines and induces apoptosis in A549 cells. NAE-IN-M22 also can inhibit tumor growth in vivo.

Cucurbitacin B (Cuc B) has profound in vitro and in vivo antiproliferative effects against human pancreatic Y cells. It inhibited AKT signaling activation through up-regulation of PTEN. Cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung Y cells.

Lonidamine (Diclondazolic Acid) is an indazole carboxylic acid derivative, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK).

Lawsone methyl ether (2-Methoxy-1,4-naphthoquinone) induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells.

1. Morusin (Mulberrochromene) possesses antitumor effects of cell lines including HT-29, A549, MCF-7, and MDA-MB-231, through suppressing STAT3 and NFκB attenuation mediated apoptosis induction. 2. Morusin possesses anti-oxidant and anti-inflammatory effects.

Acacetin (5,7-Dihydroxy-4'-methoxyflavone) is an O-methylated flavone found in various plants, shows antinociceptive, anti-inflammatory, and antioxidant activity in various research models.

Inauhzin (INZ)(INZ) is a novel small molecule that effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human Y cells without causing apparently genotoxic stress(IC50=3 uM, in A549 cell).

Sphondin has anticonvulsant, anti-inflammatory, and anti-proliferative activities, it possessed an inhibitory effect on IL-1beta-induced increase in the level of COX-2 protein and PGE(2) release in A549 cells.

Chloramphenicol (Chloromycetin), a broad-spectrum antibiotic, blocks bacterial protein synthesis.

1. Peimisine (Ebeiensine) can affect M-receptor, excit β-receptor, restrain the release of internal calcium, and promote to releaseing nitrogen monoxidum in order to relax tracheal smooth muscle and relieve asthma. 2. Peimisine can attenuate lung tissue injury( ALI), LDH and MDA amount in ALI mice in a dose dependent manner, it also lower the total protein, total white blood cells, lymphocyte and neutrophilic leukocyte in bronchoalveolar lavage fluid( BALF); suggests that peimisine can play a protective role against LPS-induced acute lung injury. 3. Peimisine has the protective effect on the experimental hepatic fibrosis formation, the possible mechanisms are associated with inhibiting fibrogenesis and fibrosis accumulation, and decreasing lipid peroxidation. 4. Peimisine can inhibit angiotensin I converting enzyme activity in a dose-dependent manner, displaying 5 % inhibitory concentration values of 526.5 microM, thus, it may have antihypertensive action.

Helichrysetin has mild anti-HIV-1 PR activity. Helichrysetin has great potentials for development as an anticancer agent, it has cytotoxic effect on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29.

WZB117 is a Glucose Transporter 1 (GLUT1) inhibitor. when IC50 of WZB117 approximate 10 μM, it inhibits lung cancer A549 cells and breast cancer MCF7 cells proliferation.

Tanespimycin (KOS 953) (17-AAG) is an inhibitor of Hsp90 that selectively inhibits BT474 tumor cell Hsp90 (IC50: 5 nM).

PROTAC NSD3 degrader-1 (compound 56) is a targeted degradation agent for the Nuclear receptor binding SET domain protein NSD3. It effectively induces the degradation of NSD3 in NCI-H1703 and A549 lung cancer cell lines, with DC50 values of 1.43 and 0.94 μM, respectively. Additionally, it hinders H3K36 methylation, triggers apoptosis, and arrests the cell cycle. Furthermore, PROTAC NSD3 degrader-1 diminishes the expression of NSD3-related genes, including CDC25A, ALDH1A1, and IGFBP.

MAT-POS-e194df51-1 is an orally active, non-covalent, non-peptide inhibitor of the SARS-CoV-2 main protease (M^pro) with an IC_50 of 37nM. It exhibits cytotoxicity, with EC_50 values of 64nM in A549-ACE2-TMPRSS2 cells and 126nM in HeLa-ACE2 cells [1].

Euphoheliosnoid A (Compound 24), a diterpenoid, significantly enhances natural killer (NK) cell-mediated cytotoxicity against H1299-luci cells and A549-luci cells at a concentration of 2.5 μM [1].

Antiproliferative Agent-39 (Compound 12) effectively inhibits the proliferation of various cancer cell lines, including A549, SNU-638, Col2, HT1080, and MCF-7, with respective IC50 values of 11, 25, 14, 11, and 6.3 μM [1].

(2,4-Dichloro-3,5-dimethoxyphenyl) methyl 6-O-β-D-glucopyranosyl-β-D-glucopyranoside, an anticancer agent, inhibits A549 lung cancer cell proliferation with an IC50 of 29 μM. This compound is derived from Lilium regale and is utilized in cancer research [1].

3-O-(E)-p-coumaroyl tormentic acid may be promising lead compound for developing an effective drug for treatment of leukemia, it induces apoptotic cell death in human leukemia (HL60) via mainly mitochondrial pathway by, at least in part, Topo I inhibition. 3-O-trans-p-coumaroyltormentic acid shows cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) in vitro, the IC50 values of 13.72, 14.29,14.61, 14.04 uM, respectively. 3beta-O-cis-p-Coumaroyltormentic acid, and 3beta-O-trans-p-coumaroyltormentic acid are weakly selective for vancomycin-resistant Enterococcus (VRE) compared with eukaryotic cells, with an MIC of 59.4microg/mL and a 50% inhibitory concentration (IC50) of 72.0microg/mL for monkey kidney epithelial (MA104) cells. A mixture of 3-O-cis-p-coumaroyltormentic acid and 3-O-trans-p-coumaroyltormentic acid shows an inhibitory effect comparable to (-)-epigallocatechin gallate (EGCG) of green tea on the activation of Epstein-Barr virus early antigen (EBV-EA) induced by 12-O-tetradeca--noylphorbol-13-acetate (TPA).

Pseudoginsenoside Rh2 has cytotoxicity, it induces mitochondrial apoptosis in A549 cells and is responsible for excessive activation of the Ras/Raf/ERK/p53 pathway. (20Z) -Pseudoginsenoside Rh2 and (20E)-Pseudoginsenoside Rh2 have antioxidative activity.

Guajadial B acts as a Top1 catalytic inhibitor and delays Top1 poison-mediated DNA damage. Guajadial B shows cytotoxicities against five human cancer cell lines, it is the most effective having an IC50 value of 150 nM toward A549 cells.

MM41 is a human telomeric and gene promoter DNA quadruplex stabilizer with an IC50 of <10 nM against the MIA PaCa-2 pancreatic cancer cell line.

Norsanguinarine has antifungal activity, it exhibits 100 % inhibition of A. brassicicola and C. maculans at 1000 ppm whereas. It shows significant cytotoxic activities (ED (50) values < 4 microg/ml) against P-388, KB16, A549, and HT-29 cell lines.

PAR2 (1-6) amide is a synthetic peptide agonist of proteinase-activated receptor 2 (PAR2) that corresponds to residues 1-6 of the amino terminal tethered ligand sequence of human PAR2 and residues 37-42 of the full-length sequence.1It binds to NCTC 2544 cells expressing human PAR2 (Ki= 9.64 μM in a radioligand binding assay) and induces calcium mobilization in the same cells (EC50= 0.075 μM).2PAR2 (1-6) amide (100 μM) reduces colony formation of A549 lung cancer cells.1It induces superoxide production and degranulation in isolated human eosinophils when used at a concentration of 500 μM.3PAR2 (1-6) amide (5 μmol/kg) induces tear secretion in rats when used in combination with amastatin .4 1.Bohm, S.K., Kong, W., Bromme, D., et al.Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2Biochem. J.314(Pt 3)1009-1016(1996) 2.Kanke, T., Ishiwata, H., Kabeya, M., et al.Binding of a highly potent protease-activated receptor-2 (PAR2) activating peptide, [3H]2-furoyl-LIGRL-NH2, to human PAR2Br. J. Pharmacol.145(2)255-263(2005) 3.Miike, S., McWilliam, A.S., and Kita, H.Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2J. Immunol.167(11)6615-6622(2001) 4.Nishikawa, H., Kawai, K., Tanaka, M., et al.Protease-activated receptor-2 (PAR-2)-related peptides induce tear secretion in rats: Involvement of PAR-2 and non-PAR-2 mechanismsJ. Pharmacol. Exp. Ther.312(2)324-331(2005)

Neoaureothin is a bacterial metabolite that has been found in Streptomyces. It is an androgen receptor (AR) antagonist that inhibits binding of dihydrotestosterone (DHT) to ARs (IC50 = 13 μM) and inhibits DHT-induced expression of prostate-specific antigen in LNCaP cells (IC50 = 1.75 nM). Neoaureothin is cytotoxic to A549, HCT116, and HepG2 cells (IC50s = 34.3, 47, and 37.2 μg/ml, respectively). It also has nematocidal activity against the pine wood nematode B. xylophilus (LC50 = 0.84 μg/ml) and increases survival of P. densiflora trees inoculated with B. xylophilus.

Urdamycin A is a bacterial metabolite originally isolated fromS. fradiaethat has antibacterial and anticancer activities.1,2It is active against a variety of Gram-positive and Gram-negative bacteria, includingB. subtilisand strains ofArthrobacterandStreptomyces, but not the fungusS. cerevisiae, in a disc assay when used at a concentration of 1 mg/ml.2Urdamycin A is cytotoxic to L1210 and HT-29, but not A549, cancer cells (IC50s = 7.5, 5, and >10 μg/ml, respectively).1

FQI 1 is a selective late-stage SV40 factor (LSF) inhibitor with anticancer activity that exerts its antiproliferative activity by disrupting the mitotic spindle.FQI 1 inhibits the proliferation of NIH/3T3, HeLa, and A549 cells, and can be used in the study of cancers.

IGF2BP1-IN-1 (Compound A11), an inhibitor of IGF2BP1, impedes the associated downstream signaling and demonstrates a high affinity for the IGF2BP1 protein with a dissociation constant (K D) of 2.88 nM. The compound effectively halts the proliferation of cancer cells, as evidenced by an IC50 of 9 nM for A549 cells and 34 nM for HCT116 cells, while also inducing apoptosis in these cells. Moreover, IGF2BP1-IN-1 has been shown to inhibit tumor growth in an A549 xenograft mouse model [1].

Compound 3a, an anticancer agent and ketone derivative, exhibits potent activity against the A549 cancer cell line, demonstrating an inhibitory concentration (IC50) of 6.62 μM [1].

Soladulcoside A, a steroidal glycoside with antineoplastic properties, is derived from the entire Solanum nigrum plant. It demonstrates inhibitory effects on A549 cells, suggesting its applicability in researching non-small cell lung cancer (NSCLC) [1].

Protoapigenone, an antineoplastic agent extracted from ferns, demonstrates notable inhibitory activity against various cancer cell lines, including Hep G2, Hep 3B, MCF-7, A549, and MDAMB-231. The respective IC50 values are 1.60, 0.23, 0.78, 3.88, and 0.27 μg/mL [1].

Euphoscopin C, a diterpenoid isolated from Euphorbia helioscopia, significantly enhances the cytotoxic activity of natural killer (NK) cells against H1299-luci and A549-luci cells [1].

Bufoserotonin C, an indole alkaloid derived from the traditional Chinese medicine Chansu, exhibits antitumor activity and demonstrates an IC50 value of 34.3 μM in A549 cells [1] [2].

Anticancer agent 33 (compound 3), derived from Squamocin and Bullatacin, exhibits potent inhibitory activity against the 4T1 breast cancer cell line (A549, HeLa, HepG2, and MCF-7 cells), with IC50 values ranging from 1.9 to 5.4 µM [1].

Anhydroepiophiobolin A is a sesterterpenoid fungal metabolite that has been found in B. oryzae. It is cytotoxic to HepG2 and K562 cells (IC50s = 47.1 and 35.6 μM, respectively) as well as A549, SKOV3, SK-MEL-2, XF498, and HCT15 cells (IC50s = 1.6-1.9 μg/ml). Anhydroepiophiobolin A is phytotoxic to S. viridis and D. erucoides in a leaf puncture assay.

Trypacidin is a fungal metabolite originally isolated fromA. fumigatus.1It is active againstB. subtilisandM. bovis(MICs = 12.5 and 1.25 μg/ml, respectively), as well asT. cruziandT. gondii(MICs = 5-10 and 10-20 μg/ml, respectively).1,2It reduces viability and induces lysis of A549 human lung cancer cells (IC50s = 7.4 μM for both).3Trypacidin increases survival in a mouse model ofT. gondiiinfection when administered in six doses of 12.5 mg/kg each.1 1.Balan, J., Ebringer, L., Nemec, P., et al.Antiprotozoal antibiotics. II. Isolation and characterization of trypacidin, a new antibiotic, active against Trypanosoma cruzi and Toxoplasma gondiiJ. Antibiot. (Tokyo)16157-160(1963) 2.Song, Z., Liu, Y., Gao, J., et al.Antitubercular metabolites from the marine-derived fungus strain Aspergillus fumigatus MF029Nat. Prod. Res.1-8(2019) 3.Gauthier, T., Wang, X., Dos Santos, J.S., et al.Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cellsPLoS One7(2)e29906(2012)

7-Prenyljacareubin shows moderate cytotoxic activity against HL-60, SMMC-7721, A549, MCF-7, and SW480 cell lines.

Thiocoraline is a depsipeptide and DNAbis-intercalator originally isolated fromMicromonosporawith antibacterial and anticancer activities.1,2It is active against the Gram-positive bacteriaS. aureus,B. subtilis, andM. luteus(MICs = 0.05, 0.05, and 0.03 μg/ml, respectively) but not Gram-negativeE. coli,K. pneumoniae, orP. aeruginosa(MICs = >100 μg/ml for all).1Thiocoraline inhibits RNA and DNA polymerase and thymidylate synthase (IC50s = 6, 6, and 15 μg/ml, respectively), as well as RNA and DNA synthesisin vitro(IC50s = 0.008 and 0.4 μg/ml, respectively). It is cytotoxic to P388, A549, HT-29, and MEL-28 cancer cells (IC50s = 0.002, 0.002, 0.01, and 0.002 μg/ml, respectively). 1.Romero, F., Espilego, F., Pérez Baz, J., et al.Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activitiesJ. Antibiot. (Tokyo)50(9)734-737(1997) 2.Negri, A., Marco, E., García-Hernández, V., et al.Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptideJ. Med. Chem.50(14)3322-3333(2007)

HT-2 Toxin, a deacetylated metabolite of T-2 toxin, impairs protein synthesis and hinders cell proliferation in plants.