Department of Pharmaceutical Chemistry
JNTUA-OTRI, Anantapur, India
The process of establishing a new drug is exceedingly complexioned involves the talents of people from a variety of disciplines including Pharmaceutical chemistry, biochemistry, physiology, pharmacology, pharmaceutics and medicine. Quinazolinone is a heterocyclic chemical compound. There are two structural isomers, 2-quinazolinone and 4-quinazolinone, with the 4-isomer being the more common. Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, anti-inflammatory, antihistaminic, anticancer CNS depressant, and so on. All the synthesized quinazolinone derivatives were confirmed preliminarily by M.P and TLC and further all the synthesized compounds were screened for anti-inflammatory activity using Phenyl butazone as the standard and carragennin induced paw oedema model used for anti-inflammatory activity.
Key words: Phenyl butazone, anti-inflammatory activity, Quinazolinone, Anthranilic acid, Ethanol.
Medicinal chemistry is concerned mainly with the organic, analytical and biological aspects of this process, but its people must interact productively with those in the other disciplines. It occupies a strategic position at the interface of chemistry and biology. There is considerable overlap with other disciplines for e.g. Medicinal chemistry and pharmacology both are concerned with mode of action and SAR of drugs. However, this kind of overlap facilities productive interactions in research.
The present survey aims to achieve the pharmacological properties quinazolinones and their derivatives. Quinazolinone has been considered as a magic moiety possessing myriad spectrum of medicinal activities. Diversity of biological response profile has attracted considerable interest of several researchers across the globe to explore this skeleton for its assorted therapeutic significance. Various novel classes of structurally different quinazolinones have been designed, synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, CNS depressant, Analgesics and anti-inflammatory, antihistaminic, anticancer and so on. Moreover, the nucleus constitutes an integral structural component in a number of drugs currently employed in several clinical therapies.
All the synthesized quinazolinone derivatives are tested for Anti-Inflammatory activity.
Male albino Wister rats weighing 200–250 g, supplied by M: s. B.N. Ghosh & co., Calcutta, India, were placed in cages with wire-net floors in a controlled room temperature 29°C, relative Humidity 60–70% and provided with food and water adlibitum. The animals were deprived of food for 24 h before experimentation but allow free access to tap water throughout. All studies were carried out by using six rats in each group.
Carrageenin-induced rat paw oedema
Oedema was induced by subplanter injection of 0.1 ml of 1% freshly prepared suspension of carrageenin into the right hind paws of the rats of four groups of six animals each. The volume of the injected and contra-lateral paws were measured 1,3 and 5 h after induction of inflammation using a plethysmometer according to the method described by Winter et al. (1962) The test groups received the synthesized comounds (200mg/kg), the standard group received phenylbutazone (100 mg:kg), and the control animals received the vehicle only. All the treatments were given intraperitoneally 30 min prior to the injection of carrageenin except for the synthesized compounds .Increase of paw edema thickness was calculated.
The results of the anti-inflammatory effect of the 200mg/kg of compounds VIIa,VIIb ,VIIc,VIId, VIIe on carragenin induced oedema in rat’s right hind paws are presented in figures2 & 3. There was a gradual increase in oedema paw volume of rats in the control (carragennin treated). However, in the test groups, treated with compounds VIIa, VIIb, VIIc, VIId, VIIe showed a significant reduction in the oedema paw volume. As shown in Table the significant anti-inflammatory effect induced by compounds appeared at 1h and progressively increased. The compounds VIIc & VIIe showed a maximum inhibition of 33.58% & 36.79% respectively at 3rd hour. The anti-inflammatory effect induced by Phenyl butazone progressively increased and reached a maximum (40.49%) at 3rd hour.
The present study establishes the anti-inflammatory activity of the compound VIIa. VIIb, VIIc,VIId, VIIe. The compounds effectively suppressed the inflammation produced by carragenin. It is evident that carragennin induced oedema is commonly used as an experimental animal model of acute inflammation and it is believed to be biphasic of which the first phase is mediated by release of histamine and serotonin in the early phase followed by kinin release and then by prostaglandin in the later phase. But the most significant anti-inflammatory response occurred at the third hour, reduction in paw edema by 33.58% & 36.79% respectively for compound VIIc & VIIe. The standard (phenylbutazone) showed a maximum response at third hour and % inhibition is recorded to be 40.49% .