Synthesis and biological evaluation of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates.

This study reports the design and synthesis of novel dialkyl (4-amino-5H-chromeno[2,3-d]pyrimidin-5-yl)phosphonates as potential antitumor agents against A549 (lung cancer), DU-145 (prostate cancer), PC-3 (prostate cancer), HeLa (cervical cancer) and MCF-7 (breast cancer), cell lines evidenced from the in vitro antitumor studies performed by MTT assay (across 10-30 µM concentrations). The structural eminence of these synthesized molecules has emanated by designing the structural core by uniting the chromene, pyrimidine and phosphonate moieties into one, which has augmented their novelty and made them unreported. Further the deep structural activity relationship study investigations articulated that the title compounds are promising drug-like compounds and potential inhibitor of histidine amino acid residue present on the respective enzymatic proteins [3QJZ (A549), 3VHE (DU-145), 3V49 (PC-3), 3F81 (HeLa), & 3R7Q (MCF-7)] of the cell lines screened and are identified as responsible for the multi-faceted antitumor activities predicted in vitro. The obtained results were further supported by molecular docking studies, QSAR, ADMET, and bioactivity studies which have supported them as potential BBB penetrable molecules and proficient CNS active neuro-protective agents during drug delivery.

Ultrasound Promoted Synthesis and Anticoagulant Activity of 2-Amino- 4H-chromen-4-ylphosphonates.

BACKGROUND: One of the alarming difficulties in the field of hematology is the Coagulant disorders. Despite the availability of clinically proven existing anticoagulants, their limitations have prompted a continuous search for novel anticoagulants. OBJECTIVE: The primary objective of the study is to synthesize a series of 2-amino-4H-chromen-4- ylphosphonate derivatives and to test their anticoagulant activity depending on PT measurements considering commercial heparin as positive control. METHOD: 2-Amino-4H-chromen-4-ylphosphonates were synthesized by the reaction of salicylaldehyde derivatives (1), malononitrile (2) and dialkyl phosphite (3) in ethanol using piperazine as a catalyst by ultra-sonication at room temperature. All the title compounds (4a-l) were tested for anticoagulant activity. RESULTS: The results of the anticoagulant activity of the title compounds revealed that 4j, 4h and 4g showed prolonged prothrombin time 87.28, 81.81 and 78.42 sec when compared with that of the standard heparin which has prothrombin time of 121.50 sec. CONCLUSION: The findings from this study highlight that ultrasonication of the one pot three component reaction of salicylaldehyde derivatives, malononitrile and dialkyl phosphite with piperazine as a catalyst for the synthesis of 2-amino-4H-chromen-4-ylphosphonates is the best method. In vitro coagulant assay in terms of prothrombin time (PT) revealed that 4j, 4h and 4g possess promising anticoagulant properties. Other compounds (4a-l) were also found to have significant anticoagulant effect when compared with the heparin as positive control. Thus, these compounds qualify for further clinical studies to be used as the blood anticoagulants.

TiO2-SO4(2-) Catalyzed Synthesis and Antimicrobial Activity / Molecular Docking Studies of ß-Indolylnitroalkanes.

Michael addition of indole derivatives with various substituted nitrostyrenes to yield ß- indolylnitroalkanes is accomplished effectively under solvent free conditions using TiO2-SO4(2-) as efficient catalyst at 60 º C. All the synthesized compounds were screened for their antibacterial activity through in silico and in vitro methods. The molecular docking studies against FabH enzyme, a potential drug target of bacterial fatty acid biosynthetic pathway indicated the scope of developing them a new class of antimicrobial agents. Among the title compounds, 5h exhibited the highest dock score and the highest antibacterial activity when compared with other compounds and the standard drug Ampicillin. In addition, the compounds 5d, 5e, 5g, 5h, 5i, 5j and 5l showed significant inhibitory activity at different dose concentrations under in vitro conditions against the specified bacterial strains thus qualifying for further clinical evaluation so that they can be used as effective anti-bacterial agents.