Microwave-assisted Facile Synthesis And Anticancer Evaluation Of N-((5-(substituted Methylene Amino)- 1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives

Abstract

Microwave induced synthesis has various advantages over conventional synthesis, such as highly accelerated reaction rate , reasonable better yields, simple open systems, no solvent or very less amount of solvents required, eco friendly method, clean heating system and control on reaction parameters .In the present work novel Schiff’s bases containing thiadiazole scaffold and benzamide group, through appropriate pharmacophore were designed and synthesized , because of the important biological properties associated with these three moieties/groups. The coupling of these important moieties was achieved under microwave irradiation. A facile, solvent-free synthesis of a series of N-((5-(substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl)benzamide was carried out under microwave-irradiation. Solvent free synthesis of novel Schiff bases was achieved by cyclo-addition of various aromatic aldehydes (0.01 mol) and N-((5-amino-1,3,4-thiadiazol-2-yl)methyl)benzamide(0.01 mol)in presence of catalytic amount of glacial acetic acid under microwave irradiation. The same compounds were also synthesized using conventional approach. The conventional method required 15-18 hrs, while microwave irradiation method required only 15-20 minutes and gave better yields. Total 12 final compounds were synthesized as per the scheme reported. Structures of synthesized compounds were confirmed by IR, NMR, and Mass spectral study. All the designed hybrids were evaluated for their in vitro anticancer activity against a panel of three human cancer cell lines viz SK-MEL-2(melanoma), HL-60 (leukemia) and MCF-7 using MTT assays method. Most of the synthesized compounds exhibited promising anticancer activity with the some compounds having GI50 values similar to that of the Adriamycin. The compounds 7k, 7l, 7b, and 7a were found to be the most promising in this study. A computational study of synthesized compounds 7(a–l) was performed for prediction of ADMET. The absorption, distribution, metabolism, excretion and Toxicity (ADMET) properties of all compounds were predicted using Qikprop v3.5 (Schrödinger LLC)