Synthesis and Antimicrobial, Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis

Abstract

In our attempt towards the synthesis and development of effective antimicrobial, anticancer and antioxidant agents, a novel series of 2,3-dihydropyrido[2,3-d]pyrimidin-4-one 7a–e and pyrrolo[2,1-b][1,3]benzothiazoles 9a–e were synthesized. The synthesis of 2-(1,3-benzo thiazol-2-yl)-3-(aryl)prop-2-enenitrile (5a–e) as the key intermediate was accomplished by a microwave efficient method. Via a new variety oriented synthetic microwave pathway, these highly functionalized building blocks allowed access to numerous fused heteroaromatic such as 7-amino-6-(1,3-benzo thiazol-2-yl)-5-(aryl)-2-thioxo-2,3dihydropyrido [2,3-d]pyrimidin-4(1H)-one 7a–e and 1-amino-2-(aryl)pyrrolo[2,1-b][1,3]benzothiazole-3-carbonitrile derivatives 9a–e in order to study their antimicrobial and anticancer activity. The present investigation offers effective and rapid new procedures for the synthesis of the newly polycondensed heterocyclic ring systems. All the newly synthesized compounds were evaluated for antimicrobial, anticancer and antioxidant activity. Compounds 7a,d, and 9a,d showed higher antimicrobial activity than cefotaxime and fluconazole while the remaining compounds exhibited good to moderate activity against bacteria and fungi. An anticancer evaluation of the newly synthesized compounds against the three tumor cell lines (lung cell NCI-H460, liver cancer HepG2 and colon cancer HCT-116) exhibited that compounds 7a, d, and 9a,d have higher cytotoxicity against the three human cell lines compared to doxorubicin as a reference drug. These compounds also exhibited higher antioxidant activity and a great ability to protect DNA from damage induced by bleomycin.

Recent insights into antibacterial potential of benzothiazole derivatives

“…Compound 80b also deduced the potent antibacterial action against studied Gram-positive bacterial strains (MIC = 4–10 µmol L –1 ) and activity was found to be similar to the reference drug. SAR analysis proved that the inclusion of thiophene-2-yl ( 78a ) and para- fluoro phenyl ( 78b and 80b ) at the 4th position of pyridopyrimidine and pyrrole moieties enhanced the antibacterial activity [ 60 ].

Scheme 17 Synthesis of pyrimidine and pyrrole containing benzothiazole derivatives ( 78a-b and 80a-b )

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Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

“…Furthermore, candidate anticonvulsant agents had been developed based on PBTA derivatives ( Figure 1 ) [ 2 ]. In addition, series of PBTAs ( Figure 1 ) were found to exhibit antibacterial, antifungal, antioxidant, and cytotoxic activities [ 3 – 4 ].…”

“…The first group of approaches to the PBTA scaffold is an annulation of benzothiazoles with a pyrrole moiety ( Scheme 1 ). It includes intramolecular cyclizations of benzothiazoles bearing a 3'-chloro substituent at C 2 position ( Scheme 1 , entries 1 and 2) [ 5 – 7 ], intramolecular catalytic carbene cascade reactions of propargyl 1,3-benzothiazol-2-yl(diazo)acetates ( Scheme 1 , entry 3) [ 12 ], dearomative [3 + 2] cycloaddition reactions of benzothiazoles with cyclopropanes ( Scheme 1 , entry 4) [ 13 – 15 ], multicomponent reactions (MCRs) of benzothiazoles, isocyanides and 2-methylidenemalonates ( Scheme 1 , entry 5) [ 16 ], 1,3-dipolar cycloadditions of N -alkylbenzothiazolium salts ( Scheme 1 , entry 6) [ 17 – 22 ], MCRs of 2-methylbenzothiazole, acetylenedicarboxylates and active methylene compounds ( Scheme 1 , entry 7) [ 23 – 25 ], MCRs of (1,3-benzothiazol-2-yl)acetonitrile, aldehydes and acylcyanides ( Scheme 1 , enry 8) [ 3 , 26 ] and reactions of 3-acyl-2,3-dihydro-1,3-benzothiazole-2-carbonitriles with acetylenedicarboxylate ( Scheme 1 , entry 9) [ 4 ].…”

Pyrimidines as Anticancer and Antiviral: Synthesis & Reactions (A Review)

“…They form the core part of Deoxyribonucleic acids (DNA) and ribonucleic acid (RNA), so they have diverse biological activities [1][2][3] . Among these activities, are anti-inflammatory [4][5][6][7] , analgesic 8,9 , antioxidant [10][11][12] , antimalarial [13][14][15] , antimicrobial activity [16][17][18][19][20] , antitumor [21][22][23][24][25][26][27][28] and antiviral [29][30][31][32][33][34][35][36] . In this investigation we surveyed the synthesis and reaction of pyrimidines with antiviral and anticancer activity through the last five years.…”