Challenging the Biginelli scaffold to surpass the first line antitubercular drugs: thymidine monophosphate kinase (TMPK) inhibition activity and molecular modelling studies.

New Biginelli adducts were rationalised, the introduction of selected anti-tubercular (TB) pharmacophores into the dihydropyrimidine (DHPM) ring of deoxythymidine monophosphate (dTMP), the natural substrate of thymidine monophosphate kinase (TMPK). Repurposing was one of the design rationale strategies for some selected mimics of the designed compounds. The anti-TB activity was screened against the M HRv strain where was superior to ethambutol (EMB), and was 9-fold more potent than pyrazinamide (PZA).

New tetrahydropyrimidine-1,2,3-triazole clubbed compounds: Antitubercular activity and Thymidine Monophosphate Kinase (TMPKmt) inhibition.

Two series of new tetrahydropyrimidine (THPM)-1,2,3-triazole clubbed compounds were designed, synthesized and screened for their antitubercular (anti-TB) activity against M. tuberculosis HRv strain using microplate alamar blue assay (MABA). The most active compounds 5c, 5d, 5e and 5f were further examined for their cytotoxicity against the growth of RAW 264.

Discovery of a novel DNA binding agent via design and synthesis of new thiazole hybrids and fused 1,2,4-triazines as potential antitumor agents: Computational, spectrometric and in silico studies.

New series of furan-thiazole hybrids (3a-f), thiazolo[2,3-c]-1,2,4-triazines (4a-f), their bioisosteres 1,3,4-thiadiazolo[2,3-c]-1,2,4-triazines (8a-d) and 1,2,4-triazino[4,3-b]-1,2,4-triazines (13a-e) were designed, synthesized and evaluated for their in vitro antitumor activities at the National Cancer Institute (NCI, USA). Among the synthesized compounds, 3d was found to exhibit promising broad spectrum antitumor activity (GI MG-MID = 14.22 µM) in a five-dose assay against the full panel NCI-cancer cell lines.

Synthesis, modeling and biological evaluation of some pyrazolo[3,4-d]pyrimidinones and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones as anti-inflammatory agents.

New pyrazolo[3,4-d]pyrimidinone and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinone derivatives were synthesized. They have been evaluated for their anti-inflammatory activity using in vitro (COX-1/COX-2) inhibitory assay. Moreover, compounds with promising in vitro activity and COX-1/COX-2 selectivity indices were subjected for in vivo anti-inflammatory testing using formalin induced paw edema and cotton-pellet induced granuloma assays for acute and chronic models, respectively.

Structure-based design of some isonicotinic acid hydrazide analogues as potential antitubercular agents.

New pyridine derivatives were designed and synthesized as Isonicotinic acid hydrazide (INH) analogues. The synthesized compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis strain HR. Ten compounds (3c, 3e-g, 5a-c, 6h, 10 and 11b) showed promising antitubercular activity with MIC range 7.