Synthesis of 5-arylidine amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamides endowed with potent antioxidants and anticancer activity induces growth inhibition in HEK293, BT474 and NCI-H226 cells.

ABSTRACT: A series of imines 5-amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamide derivatives were synthesized from various aromatic aldehydes and substituted with benzoyl acetazolamides under different reaction conditions and were evaluated for their antioxidant and free radical scavenging, antimitotic activity by Allium cepa meristem root model and cytotoxicity activity against HEK 293 (human epidermal kidney cell line), BT474 (breast cancer cell line) and NCI-H226 (lung cancer cell line) by MTT assay. Some of the synthesized compounds showed moderately potent cytotoxicity compared to indisulam. GRAPHICAL ABSTRACT: A series of imines 5-amino-1,3,4-thiadiazol-2-[(N-substituted benzyol)]sulphonamide derivatives (9a-j); 5-amino-1,3,4-thiadiazol-2-[N-(substituted benzoyl)]sulphonamide (4a-g); 5-(4-acetamido phenyl sulphonamido)-1,3,4-thiadiazol-2-[N-(substituted benzoyl)]sulphonamide (6a-g); and 5-(4-amino phenyl sulphonamido)-1,3,4-thiadiazol-2-[N-(substituted benzoyl)]sulphonamide (7a-g) were synthesized from acetazolamide and were investigated for the in vitro anticancer by MTT assay, free radical scavenging and antimitotic activity by Allium cepa root meristem model. Experimental observations indicate that synthesized compounds were moderately potent anticancer agents.

Structure-based design, synthesis and molecular modeling studies of thiazolyl urea derivatives as novel anti-parkinsonian agents.

Synthesis of 1-(substituted aryl)-3-(thiazol-2-yl)urea derivatives was undertaken as our efforts to discover novel antiparkinsonian agents with improved pharmacological profile in haloperidol-induced catalepsy and oxidative stress in mice. Furfuryl, 2- and/or 3-methoxy substituted phenyl derivatives emerged as potent agents. With exception of 2-chloro,5-trifluoromethyl substituted analog, halogen substituted derivatives exhibited moderate antiparkinsonian activity. The results of biochemical investigations from brain homogenate of mice outline the importance of neuroprotective/antioxidant therapy for Parkinson's disease (PD), supporting the notion that the oxidative stress may play a significant role in the pathophysiological mechanisms underlying PD. Molecular docking studies of these compounds with adenosine A(2A) receptor exhibited very good binding interactions and warrants further studies to confirm their binding with human A(2A) receptor for the design and development of potent antagonists. Parameters for Lipinski's rule of 5 were calculated computationally because pharmacokinetic and metabolic behaviors in the body often are linked to the physical properties of a compound. None of the synthesized compounds violated Lipinski's rule, making them suitable drug candidate for the treatment of PD.