A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities.
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 (IC501.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50<1.56μM) and 6l (IC50=2.87μM) 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 IC50values of 1.10 and 1.16μmol/L respectively.
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India.
Chelliah
C
Bharkavi
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India.
Sundaravel
S
Vivek Kumar
School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan 301030, India.
Mohamed
M
Ashraf Ali
School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Hasnah
H
Osman
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India. Electronic address: muthumanian2001@yahoo.com.
Shanmugam
S
Muthusubramanian
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India. Electronic address: subbu.perum@gmail.com.
Subbu
S
Perumal
D000110:Acetylcholinesterase / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D002867:Chromones; D007192:Indenes; D011759:Pyrrolidines; D013141:Spiro Compounds; D013844:Thiazoles; D000110:Acetylcholinesterase; C032519:pyrrolidine
1,3-Dipolar cycloaddition; AchE inhibition; Azomethine ylides; CCRF-CEM; Dispiro heterocycles; M. tuberculosis H(37)Rv