Synthesis, in silico and in vitro anti-cancer studies of phosphorylated derivatives of didanosine targeting MDA-MB-231 breast cancer cell lines.

A series of new phosphorylated derivatives of didanosine were designed, synthesized and evaluated their anticancer effects on human breast cancer cells. Their binding affinities were evaluated against aromatase enzyme and the molecular docking studies demonstrated that 9a, 9h and 9i exhibited high binding interactions than the parent molecule (ddI) and other derivatives; evaluated the aromatase enzyme inhibition. The cell viability, cell proliferation, lactate dehydrogenase showed potential anti-proliferative in dose dependent manner, these results were well correlated with hoesch stain and DNA fragmentation on MDA-MB-231 breast cancer cell lines. Cytotoxicity results disclosed that tryptophan amino acid ester substituted derivative 9i showed potential cell death against MDA-MB-231 cancer cell lines. Furthermore, compound 9i has great potential significance for further investigations (in vivo).

Design, synthesis, characterization and in vitro, in vivo and in silico antimicrobial and antiinflammatory activities of a new series of sulphonamide and carbamate derivatives of a nebivolol intermediate.

A series of new sulphonamide and carbamate derivatives of Nebivolol drug intermediate (5) were designed and synthesized by reacting various biopotent sulphonylchlorides and chloroformates. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and mass) and screened for their in vitro antimicrobial activity against four bacterial and three fungal strains, in vitro and in vivo antiinflammatory activity against LPS-induced inflammation in RAW 264.7, in vitro COX-1 and COX-2 inhibition potentiality, antagonistic profiles of carrageenan induced paw edema and cotton pellet induced granuloma in rat. Further, the compounds were screened for their antimicrobial and antiinflammatory activity against DNA gyrase A, COX-1 and COX-2 by using molecular docking approach. The bioactivity and toxicity risks were analysed through Molecular Operating Environment. The results revealed that the compounds 8b, 8c, 8d, 8e, 8f, 8g and 9a exhibited the most promising antimicrobial activity against all the bacterial and fungal strains tested when compared with the standard drugs streptomycin and fluconazole. In view of in antiinflammatory activity, the compounds, 8b, 8c, 8d, 8e, 8f, 8g and 9a have shown potent antiinflammatory activity by inhibiting the LPS-induced inflammation in RAW 264.7 cell line, concentration dependent inhibition of COX-1 and COX-2, dose response dependent antagonism of carrageenan induced paw edema and granuloma tissue in rat. Molecular docking, ADMET and QSAR studies predicted that the recorded in silico profiles are in strong correlation with in vitro and in vivo antimicrobial and antiinflammatory results. In addition, the elevated toxicology risks of the title compounds are identified with in the potential limits of drug candidates. Hence, it is suggested that the synthesized derivatives will stand as the promising antimicrobial and anti-inflammatory drug candidates in future.

PEG-SO(3)H catalyzed synthesis and cytotoxicity of α-aminophosphonates.

One pot three-component PEG-SO(3)H catalyzed reaction of 4-(Pyridin-4-yl)benzaldehyde and triethyl phosphite with various primary amines afforded α-aminophosphonates with high yields by the Kabachnik-Field's reaction. These new structurally diversified set of α-aminophosphonates (4a-j) were evaluated for their anti-tumor activity on human chronic myeloid leukemia cells (K 562), human colon carcinoma cells (Colo 205) along with non-cancerous human embryonic kidney cells (HEK 293). They showed moderate activity on both cancerous cells and non-cancerous cells.

6-Bromo-2-(4-nitro-phen-oxy)-3-(1-phenyl-ethyl)-3,4-dihydro-1,3,2-benzoxaza-phosphinine 2-oxide.

In the title compound, C(21)H(18)BrN(2)O(5)P, the six-membered oxaza-phosphinine ring is in a twist-boat conformation. One of the phosphoryl O atoms is in an equatorial configuation while the other is axial with respect to the oxaza-phosphinine ring. The mean planes of the benzene ring to which the nitro group is attached and the phenyl ring form a dihedral angle of 83.5 (1)°. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into chains along [100].

2,4,8,10,13-Penta-methyl-6-phenyl-13,14-dihydro-12H-6λ-dibenzo[d,i][1,3,7,2]dioxaza-phosphecin-6-thione.

In the title compound, C(25)H(28)NO(2)PS, the cyclo-decene ring exhibits a crown conformation. The two dimethyl-benzene rings which are fused symmetrically on either side of the ten-membered ring, make dihedral angles of 20.2 (1) and 18.0 (1)°. The phenyl ring substituted at P is perpendicular to the heterocyclic ring, making a dihedral angle of 88.4 (1)°. The crystal structure is stabilized by very weak intra-molecular C-H⋯O hydrogen bonding.