Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease

Table 1 Methylxanthines compared with common chitinase inhibitors in IC₅₀

Compound name	Chemical formula	IC50	Ref.
Caffeine	C8H10N4O2	469 ± 23 μmol/L against Aspergillus fumigatus (A. fumigatus) chitinase	[10]
Pentoxifylline	C13H18N4O3	126 ± 7 μmol/L against A. fumigatus chitinase	[10]
Theophylline	C7H8N4O2	1500 ± 90 μmol/L against A. fumigatus chitinase	[10]
Allosamidin	C25H42N4O14	10 μmol/L against Candida albicans chitinase	[42]
Argifin	C29H41N9O10	3.7 μmol/L against Lucilia cuprina (L. cuprina) chitinase	[78]
Argadin	C29H42N10O9	3.4 nmol/L at 20 °C against L. cuprina chitinase	[79]

IC₅₀: The half maximal inhibitory concentration.

Table 2 Major biological effects of methylxanthine derivatives

Compound	Molecular weight (g/mol)	Biological effects	Side effects
Caffeine	194.19	Increases alertness, slightly increases metabolic rate[80], increases blood pressure, is a diuretic, improves sports performance[81]	Caffeine dependency, restlessness, insomnia, and anxiety at high levels (250-500 mg daily[82])In extreme amounts (> 600 mg daily chronically): Gastrointestinal (GI) disturbance1, irregular/rapid heartbeat, mania, depression, and psychosis[83]
Pentoxifylline	278.31	Improves blood circulation through peripheral blood vessels, prevents nausea/ altitude sickness, improves red blood cell deformability (i.e., sickle cell anemia), reduces blood viscosity, reduces formations of platelet aggregation/thrombus[84]	Irregular heartbeat, chest pain, dizziness, edema in extremitiesAcute toxicity in rats determined at 1772 mg/kg[85]
Theophylline	180.164	Relaxes bronchial smooth muscle, increases heart contractility, rate, and efficiency, increases blood pressure, increases renal circulation, stimulates respiratory center of CNS, treatment for COPD, asthma, infant apnea[86,87]	Interactions with many drug (cimetidine and phenytoin), and causes nausea, arrhythmias, insomnia, irritability, dizziness, seizures and tachyarrhythmias at toxic concentrations (> 20 mg/mL)[86]

¹GI disturbance is marked by nausea, vomiting, abdominal pain, diarrhea, bowel incontinence, and anorexia. COPD: Chronic obstructive pulmonary disease; CNS: Central nervous system.