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Fused Heterocyclic compounds an important skeleton for pharmaceutical is the most privileged and predominate of organic chemistry. They have formidable medical value and pharmaceutical effectiveness. Actually, in this study the mean units building (1 and 2) represented by N-substituted 1,2,4-triazole have been successfully prepared through clickmulticomponent reaction among glycine (creatinine) thiosemicarbazide and vanillin using the grinding technique as a green approach for only (15 min) in acidic media from freshly prepared lemon juice as a highly selective and biocatalyst. Then, a green and ecofriendly strategy used to afford a new series of fused quinazolinones (3-10) using the above units building (1 and 2) via also click-Multicomponent reactions with anthranilic acid and substituted acid chloride in basic media from triethylamine and the reaction was accelerated by microwave radiation for (20-60 sec) at (450 Watt) in good to excellent yield. The anticancer evaluation has been done successfully for compounds (4 and 7) against breast and lung cancer cells (human cells) and also they shown high growth inhibition with the low cytotoxicity.