Wednesday , 21 October 2020

ANALGESIC ACTIVITY OF 3-[(5-SUBSTITUED) – 1, 3, 4 OXADIAZOLE-2-YL) METHYL AMINO]-2-METHYL QUINAZOLIN-4(3H)-ONES

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About author :
Ramesh Dhani
Department of Pharmaceutical Chemistry
JNTUA-OTRI, Anantapur, India
E-mail: dhanipharmachem@gmail.com

ABSTRACT: 
Heterocyclic drug having wide spectrum of activity, Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, CNS depressant, anti-inflammatory, antihistaminic, anticancer and so on. All the synthesized quinazolinone derivatives were confirmed preliminarily by M.P and TLC and further compounds were screened for analgesic activity using acetyl salicylic acid as standard and the synthesized quinazolinone derivatives showing significant activity & hot-plate latency assay was used for the determining analgesic activity.
Key words: Acetyl salicylic acid, Hot-Plate Latency assay, Quinazolinone, Anthranilic acid, Ethanol.
Introduction :
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.A number of alkaloids having quinazoline or quinazolinone moiety in their structure have been isolated from different plants. The compounds have been found to posses useful physiological properties. 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, 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.
Materials & Methods :
Analgesic activity:
Albino mice 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 ad libitum. The animals were deprived of food for  24 hours before experimentation but allowed free access to tap water throughout. All studies were carried out by using three rats in each group
Hot plate latency assay in mice
Experimental procedure:
Experiments were carried out according to method described by Adzu et al., (2001). Mice that showed nociceptive responses within 20s when placed on hot plate maintained at 55 + 0.50c were selected and grouped into seven groups of (n=6). Group 1 was treated with saline: groups 2-6 received 200mg/kg p.o. of the synthesized compounds while group 7 received 100mg/kg of acetyl salicylic acid p.o. Each mice was placed singly on the hot plate and the latency to exhibit thermal stimulus were determined at 0h, .5h, 1h and  2h before and after the treatment. Licking of paws and jumping were the parameters evaluated s the thermal stimulus. Sixty seconds was taken as the cut-off time to avoid mouse tissue damage.
Analgesic activity was expressed as mean percent maximal effect calculated as
% MPE = Post-drug latency—Pre-drug latency/cut-off time-Pre-drug latency
Results :
Analgesic activity of all the compounds were carried out using hot-plate latency in mice model. Treatment with 100 mg/kg of the synthesized compound significantly (P<0.05) significantly (P<0.05) protected the animals from the thermal stimuli. The percentage protections of the animal by the compounds from the thermal stimuli were comparable to that of ASA. The latencies were found to be 31.35%, 33.0%, 38.91%, 34.91% and 43.42% for compound VIIa, VIIb, VIIc, VIId and VIe respectively. Compound VIIe & VIIc showed the latency time almost to the same degree as aspirin (48.91%).
Discussion:
For the antinociceptive activity, the results (figure. 2) showed that the compounds significantly increased the pain threshold to hot-plate in Mice, which suggested that the extract displayed peripheral analgesic effect. Compounds VIIe & VIIc showed maximum % protection in hot-plate test, which suggested that the compound acted like non-steroidal anti-inflammatory drugs such as acetylsalicylic acid and the analgesic effect, may attribute to its anti-inflammatory action.On the basis of the results obtained it can be concluded that compound VIIe and compound VIIc  possessed evident analgesic activity than other compounds. On observing the results of the above experiments it is evident that compound VIIe & compound VIIc possess analgesic activity comparable with that of the acetyl salicylic acid and hence only these two compounds are screened for anti-inflammatory activity.

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