{"id":429,"date":"2015-01-22T09:05:17","date_gmt":"2015-01-22T09:05:17","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=429"},"modified":"2020-04-25T05:37:59","modified_gmt":"2020-04-25T05:37:59","slug":"analgesic-and-antidepressant-activities-of-benzothiazole-benzamides","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol1no2\/analgesic-and-antidepressant-activities-of-benzothiazole-benzamides\/","title":{"rendered":"Analgesic and Antidepressant Activities of Benzothiazole-Benzamides."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Benzothiazole derivatives in recent years have acquired conspicuous significance due to their wide spectrum of biological activities including anticonvulsant, analgesic, and antidepressant activities.1,2 <\/sup>Benzamides on the other hand had also been found to show a wide range of pharmacological activities such as anticonvulsant3<\/sup>, anti-inflammatory, 4<\/sup> analgesic, 5<\/sup> and antidepressant activity. 6<\/sup><\/p>\n

The present series was designed previously by combining the two pharmacologically active pharmacophores to get benzothiazole-benzamide derivatives and their anticonvulsant activity of them has been reported.7<\/sup><\/p>\n

Since the results were found very encouraging, we intended to test these compounds for other pharmacological activities. This paper presents the analgesic and antidepressant activities of the synthesized benzothiazole-benzamides (Fig. 1).<\/p>\n\n\n\n
\u00a0\"Figure<\/td>\nFigure 1: General structure for the synthesized compounds (1-6).<\/strong><\/p>\n

 <\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Materials and Methods<\/strong><\/p>\n

Analgesic activity<\/strong><\/p>\n

The analgesic activity was assessed by using Thermal stimulus technique.8<\/sup> The investigations were done on albino mice in groups of 6 each which were kept under standard laboratory conditions. The test compounds were suspended in methyl cellulose-water (0.5 %) mixture. Each compound was administered orally at a dose of 20 mg\/kg. The analgesic activity was assessed after 4 h interval of the administration. Tail of each mice was gently immersed into thermostatically controlled water at 55 \u00b0C. The parameter measured in test samples was time that elapsed between immersion and the attempt to withdraw the tail from hot water for control as well as treated group of animals.<\/p>\n

Antidepressant activity<\/strong><\/p>\n

The antidepressant activity was studied on albino rats of either sex (110-140 g) in group of 6 each by forced swimming test\/despair swim test.9<\/sup> The forced swimming test consisted of placing rats, individually in plexiglass cylinders (40 cm high, 20 cm in diameter) containing water (24-26 \u00b0C, 30 cm deep) for two swimming sessions: an initial 15 min training session, which was followed 24 h later, by a 5 min test session after 1 h of drug administration, the animals were removed from the cylinder dried with paper towels, placed in an individual cage to rest and recover for 15 min and was noted. Immobility time is the time spent by rat floating in water without struggling, making those movements necessary to keep the head above the water.<\/p>\n

Results and Discussion<\/strong><\/p>\n

Computational parameters<\/strong><\/p>\n

Various computational parameters were calculated by using software ACD labs version 8.0 and the values are presented in Table 1. All the values were found to be in acceptable range. Fig 2 depicts the 3D optimized general structure of the synthesized compounds.<\/p>\n\n\n\n
\u00a0\"Figure<\/td>\nFigure 2: Three dimensional optimized general structure of the synthesized N<\/em>-(6-substituted-1,3-benzothiazol-2-ylcarbamothioyl)-2\/4-substituted benzamides (1-6)<\/strong><\/p>\n

 <\/p>\n

\u00a0Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u00a0<\/strong><\/p>\n

Table 1: Computational data of compounds (1-6)<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
Compound<\/strong><\/td>\na<\/sup>Molar Refractivity (cm3<\/sup>)<\/strong><\/td>\nb<\/sup>Molar Volume (cm3<\/sup>)<\/strong><\/td>\nc<\/sup>Index of Refraction<\/strong><\/td>\nd<\/sup>Surface Tension (dyne\/cm)<\/strong><\/td>\ne<\/sup>Density (g\/cm3<\/sup>)<\/strong><\/td>\nf<\/sup>Polarizability (cm3<\/sup>)<\/strong><\/td>\n<\/tr>\n
1<\/strong><\/td>\n90.65<\/td>\n219.6<\/td>\n1.763<\/td>\n76.4<\/td>\n1.508<\/td>\n35.93<\/td>\n<\/tr>\n
2<\/strong><\/td>\n100.23<\/td>\n243.5<\/td>\n1.790<\/td>\n80.1<\/td>\n1.752<\/td>\n40.93<\/td>\n<\/tr>\n
3<\/strong><\/td>\n95.55<\/td>\n231.5<\/td>\n1.762<\/td>\n76.6<\/td>\n1.579<\/td>\n37.87<\/td>\n<\/tr>\n
4<\/strong><\/td>\n100.24<\/td>\n243.5<\/td>\n1.790<\/td>\n80.1<\/td>\n1.752<\/td>\n40.93<\/td>\n<\/tr>\n
5<\/strong><\/td>\n95.55<\/td>\n231.5<\/td>\n1.762<\/td>\n76.6<\/td>\n1.579<\/td>\n37.83<\/td>\n<\/tr>\n
6<\/strong><\/td>\n104.02<\/td>\n263.4<\/td>\n1.719<\/td>\n67.7<\/td>\n1.417<\/td>\n41.23<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

All properties are calculated from ACD labs version 8.0.a<\/sup>Molar refractivity within \u00b1 0.3 cm3<\/sup> range; b<\/sup>Molar volume within \u00b1 0.3 cm3 <\/sup>range; c<\/sup>Index of refraction within \u00b1 0.02 range; d<\/sup>Surface tension within \u00b1 0.3 dyne\/cm range; e<\/sup>Density within \u00b1 0.06g\/ cm3 <\/sup>range; f<\/sup>Polarizabilty within \u00b1 0.5 \u00d7 10-24<\/sup> cm3 <\/sup>range.<\/p>\n

Analgesic activity<\/strong><\/p>\n

All the compounds showed promising analgesic activity when tested and compared with the standard drug diclofenac and the results are presented in Table 2. Compounds 3 and 4 were found to be highly potent with p < 0.001, whereas, compounds 1, 2, 5 and 6 showed significant analgesic activity with p < 0.01.<\/p>\n

Table 2: Analgesic and antidepressant activities of compounds (1-6).<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
Compound<\/strong><\/td>\nAnalgesic activitya<\/sup><\/strong><\/td>\nAntidepressant activity<\/strong>b<\/sup><\/td>\n<\/tr>\n
Mean \u00b1 SEMc<\/sup><\/strong><\/td>\nMean \u00b1 SEMd<\/sup><\/strong><\/td>\n<\/tr>\n
Control<\/strong><\/td>\nTreated<\/strong><\/td>\nControl<\/strong><\/td>\nTreated<\/strong><\/td>\n<\/tr>\n
1<\/strong><\/td>\n11 \u00b1 1.40<\/td>\n19.0 \u00b1 1.840**<\/td>\n34.4 \u00b1 1.490<\/td>\n24.0 \u00b1 1.640<\/td>\n<\/tr>\n
2<\/strong><\/td>\n2.9 \u00b1 0.341<\/td>\n4.4 \u00b1 0.461**<\/td>\n42.0 \u00b1 1.267<\/td>\n22.6 \u00b1 1.002***<\/td>\n<\/tr>\n
3<\/strong><\/td>\n3.6 \u00b1 0.477<\/td>\n7.7 \u00b1 0.470***<\/td>\n34.6 \u00b1 1.670<\/td>\n25.0 \u00b1 1.433*<\/td>\n<\/tr>\n
4<\/strong><\/td>\n2.2 \u00b1 0.177<\/td>\n5.4 \u00b1 0.481***<\/td>\n48.2 \u00b1 2.504<\/td>\n38.0 \u00b1 2.378**<\/td>\n<\/tr>\n
5<\/strong><\/td>\n2.7 \u00b1 0.524<\/td>\n6.1 \u00b1 0.663**<\/td>\n39.8 \u00b1 1.332<\/td>\n24.6 \u00b1 1.484**<\/td>\n<\/tr>\n
6<\/strong><\/td>\n2.7 \u00b1 0.521<\/td>\n6.8 \u00b1 0.660**<\/td>\n23.2 \u00b1 0.827<\/td>\n16.8 \u00b1 0.942***<\/td>\n<\/tr>\n
Diclofenac<\/strong><\/td>\n1.8 \u00b1 0.20<\/td>\n19.6 \u00b1 0.890***<\/td>\n\u2014<\/td>\n\u2014<\/td>\n<\/tr>\n
Fluoxetine<\/strong><\/td>\n\u2014<\/td>\n\u2014<\/td>\n193.6 \u00b1 0.640<\/td>\n24.2 \u00b1 4.99***<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

n = 6; a<\/sup>Dose = 20 mg\/kg (p.o.); b<\/sup>Dose = 30 mg\/kg (p.o.) c<\/sup>Mean average reaction time (sec.); d<\/sup>Mean average immobility time (sec). *p < 0.05, **p < 0.01, ***p < 0.001. Data was analyzed by student\u2019s unpaired \u2018t\u2019 test.<\/p>\n

 <\/p>\n

Antidepressant activity<\/strong><\/p>\n

Antidepressant activity of all the titled compounds was evaluated and the results are shown in Table 2. Compounds 2 and 6 showed significant decrease in the immobility time and were found to be highly potent (p < 0.001) comparable with the standard drug fluoxetine. Compounds 4 and 5 were also found to be having significant antidepressant activity with p < 0.01. Results of the rest of the compounds were not significant.<\/p>\n

Conclusion<\/strong><\/p>\n

A newer series of compounds were synthesized and evaluated as analgesics and antidepressant agents. Some compounds have shown encouraging activities and are needed to be investigated further to get better agents that can have strong future commitments.<\/p>\n

Acknowledgments<\/strong><\/p>\n

Financial assistance provided by University Grants Commission (UGC) is gratefully acknowledged.<\/p>\n

\u00a0Referencess<\/strong><\/p>\n

    \n
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  10. Winter, C. A., Risley, E. A. and Nus, G. N. \u201cCarrageenan induced edema in hind paw of the rat as an assay for anti-inflammatory drugs.\u201d Soc. Exp. Biol<\/em>. 111, 544-546 (1962).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Benzothiazole derivatives in recent years have acquired conspicuous significance […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5],"tags":[],"class_list":["post-429","post","type-post","status-publish","format-standard","hentry","category-vol1no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/429","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=429"}],"version-history":[{"count":6,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/429\/revisions"}],"predecessor-version":[{"id":32882,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/429\/revisions\/32882"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=429"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=429"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=429"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}