A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

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• 作者：Chelliah Bharkavi^a ; ^&dagger ; ; Sundaravel Vivek Kumar^a ; ^&dagger ; ; Mohamed Ashraf Ali^b ; ^c ; Hasnah Osman^b ; Shanmugam Muthusubramanian^a ; ^{muthumanian2001@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Subbu Perumal^a ; ^{subbu.perum@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：1 ; 3-Dipolar cycloaddition ; Dispiro heterocycles ; Azomethine ylides ; M. tuberculosis H37Rv ; CCRF-CEM ; AchE inhibition
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 November 2016
• 年：2016
• 卷：24
• 期：22
• 页码：5873-5883
• 全文大小：1378 K

文摘

A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole–thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC₅₀ 1.07 μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC₅₀ <1.56 μM) and 6l (IC₅₀ = 2.87 μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC₅₀ values of 1.10 and 1.16 μmol/L respectively.