In:
International Journal of Pharmacy and Pharmaceutical Sciences, Innovare Academic Sciences Pvt Ltd, Vol. 8, No. 9 ( 2016-09-01), p. 224-
Abstract:
〈 p 〉 〈 strong 〉 Objective: 〈 /strong 〉 Chalcones are one of the major classes of the natural products, which display a wide range of pharmacological properties. Also, chalcones are well-known intermediates for synthesizing various heterocyclic compounds like pyrazoline and pyrimidine derivatives. The present work is designed to synthesize new 3-indolylheterocycles starting from 〈 em 〉 N 〈 /em 〉 -benzyl and 〈 em 〉 N 〈 /em 〉 -benzoyl-1 〈 em 〉 H 〈 /em 〉 -indole-3-carboxaldehyds and evaluating theirs 〈 em 〉 in vitro 〈 /em 〉 antimicrobial activity. In addition, the probability of the most promising antimicrobial compounds to inhibit ATPase, enoyl reductase and dihydrofolate reductase were studied theoretically 〈 em 〉 via 〈 /em 〉 molecular docking. 〈 /p 〉 〈 p 〉 〈 strong 〉 Methods 〈 /strong 〉 〈 strong 〉 : 〈 /strong 〉 〈 strong 〉 〈 /strong 〉 A new series of 3-indolylchalcones 2a,b were prepared and allowed to react with hydrazine hydrate, phenyl hydrazine, hydroxylamine, urea, thiourea and guanidine to afford the corresponding pyrazoles 3a,b-6a,b and pyrimidines derivatives 7a,b-9a,b. On the other hand, the reaction of 2a, b with malononitrile afforded 10a, b, which upon cyclo-condensation with formic acid, formamide, urea or thiourea yielded the fused pyrido [2,3- 〈 em 〉 d 〈 /em 〉 ]pyrimidine 11a,b-14a,b. Moreover, cyclo-condensation of 2a, b with thiosemicarbazide gave pyrazolin-1-carbothioamides 15a, b, which under cyclization with phenacyl bromide afforded thiazole derivatives 16a and 16b. While the reaction of 2a, b with cyano thioacetamide afforded 2-mercaptonicotinonitriles 17a, b. The reaction of 17a, b with some halo-compounds gave S-alkyl derivatives 18a-d and 19a-d, respectively,which under heating in the presence of piperidine gave the fused thienopyridines 20a-d and 21a-d, respectively. All the newly prepared compounds were evaluated for their 〈 em 〉 in vitro 〈 /em 〉 antimicrobial activity. In addition, molecular docking study of the most promising antimicrobial compounds against ATPase, enoyl reductase and dihydrofolate reductase theoretically is discussed. 〈 /p 〉 〈 p 〉 〈 strong 〉 Results: 〈 /strong 〉 Compounds 17a and 17b were found to be the most potent compounds with MIC of 0.98, 0.49 and 0.98µg/ml against 〈 em 〉 S. 〈 /em 〉 〈 em 〉 〈 /em 〉 〈 em 〉 pneumoniae 〈 /em 〉 〈 em 〉 〈 /em 〉 (RCMB 010010), 〈 em 〉 E 〈 /em 〉 〈 em 〉 . coli 〈 /em 〉 (RCMB 010052) and 〈 em 〉 A. 〈 /em 〉 〈 em 〉 fumigatus 〈 /em 〉 (RCMB 02568), respectively compare to the reference drugs. Also, compounds 17a and 17b exhibited good docking scores and could act as inhibitors of enzymes understudied. 〈 /p 〉 〈 p 〉 〈 strong 〉 Conclusion: 〈 /strong 〉 Further work is recommended to confirm the ability of compounds 17a and 17b to inhibit ATPase, enoyl reductase and dihydrofolate reductase in a specific bioassay. 〈 /p 〉
Type of Medium:
Online Resource
ISSN:
0975-1491
DOI:
10.22159/ijpps.2016v8i9.13184
Language:
Unknown
Publisher:
Innovare Academic Sciences Pvt Ltd
Publication Date:
2016
detail.hit.zdb_id:
2503459-5
SSG:
15,3
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