AZD1236 is a potent and reversible inhibitor of human MMP-9 and MMP-12 (IC50 = 4.5 and 6.1nM, respectively), with >10-fold selectivity to MMP-2 and MMP-13 and >350-fold selectivity to other members of the enzyme family. AZD1236 activity is approximately 20 to 50-fold lower at the rat, mouse, and guinea pig orthologues. In acute models of lung injury, AZD1236 inhibited the haemorrhage and inflammation induced by instillation of human MMP-12 into rat lungs by ~80% at 0.81mg/kg, and also abolished macrophage infiltration into BAL fluid induced by tobacco smoke inhalation in the mouse.
Anabasine HCl is used as a clinical biomarker for tobacco smoke exposure and as an insecticide. It is also a depolarizing NMJ blocker, aromatase inhibitor, nAChr antagonist, and teratogen found in species of Nicotiana.
Piriprost is a leukotriene inhibitor attenuates the smoke-induced increase in alveolar-capillary barrier permeability and decrease in plasminogen activator activity and causes a swelling of type I alveolar epithelium.
PON-PC, an oxidized phospholipid with a 9-carbon fatty acyl chain ending in an aldehyde at the sn-2 position, arises from the oxidation of palmitoyl oleoyl phosphatidylcholine (POPC) or through interaction with ozone in pulmonary surfactant. It is found in oxidized LDL. At a 40 µM concentration, PON-PC diminishes the production of TNF-α, nitric oxide (NO), and NADP+ in primary mouse alveolar macrophages and lowers the bactericidal capability of RAW 264.7 cells. Additionally, levels of PON-PC increase in the bronchoalveolar lavage fluid (BALF) of mice exposed to cigarette smoke or in older mice.
N’-Nitrosonornicotine is a tobacco-specific N-nitrosamine and carcinogen that has been found in unburned tobacco and cigarette smoke.1It induces the formation of DNA adducts in isolated rat nasal mucosa and esophagus. N’-Nitrosonornicotine induces tumor formation in rat esophagus and nasal cavity, mouse lung, forestomach, and trachea, and hamster trachea and forebrain. Urinary levels of N’-nitrosonornicotine are positively correlated with the risk of esophageal cancer in smokers.2 1.Hecht, S.S.Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosaminesChem. Res. Toxicol.11(6)559-603(1998) 2.Yuan, J.-M., Knezevich, A.D., Wang, R., et al.Urinary levels of the tobacco-specific carcinogen N’-nitrosonornicotine and its glucuronide are strongly associated with esophageal cancer risk in smokersCarcinogenesis32(9)1366-1371(2011)
Cholesteryl palmitoleate, a cholesterol ester, exhibits elevated plasma levels in ApoE- - mice following exposure to cigarette smoke and in pediatric patients diagnosed with biliary atresia. It serves as a standard for identifying cholesterol esters in human meibomian gland secretions.
Karrikinolide, a phytoreactive compound derived from smoke, holds potential in horticulture, ecological restoration, and agriculture. This compound exhibits regulatory properties by influencing endogenous cytokinin concentrations and stimulating plant growth.
Liquiritin apioside has antioxidant property by inducing glutathione (GSH) biosynthesis via the inhibition of cytokines and protected lung epithelial cells against cigarette smoke-mediated oxidative stress, might be as protective agent against epithelial
β-Cembrenediol (β-CBT) is a natural product from tobacco plants that is found in cigarette smoke condensate. β-CBT inhibits induction of the early antigen of Epstein-Barr virus (EA-EBV) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro (IC50 = 21.9 μM). It inhibits tumor promoting effects of TPA on 7,12-demethylbenz[a]anthracene-induced papilloma formation in vivo. β-CBT is also released into soil by flue-cured tobacco plants and exerts autotoxicity as well as phytotoxic activity against L. sativa seedlings.
1,6-Anhydro-D-galactose is a carbohydrate found in liquid smoke flavorings that is used as a tracer of the contribution of biomass burning to total atmospheric particulate matter.
5-Methylchrysene, a carcinogenic polycyclic aromatic hydrocarbon with four fused rings, functions as an aryl hydrocarbon receptor agonist. It is generated through the incomplete combustion of organic matter and primarily detected in gasoline exhaust and tobacco smoke. Additionally, 5-Methylchrysene can be converted into mutagenic metabolites by cytochrome P450 enzymes 1A1 and 1B1.