Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies.

Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ±â€¯0.01 to 18.50 ±â€¯0.90 µM when compared with the standard inhibitor thiourea having IC50 value 21.25 ±â€¯0.90 µM. Among the series, analog 9 (0.14 ±â€¯0.01 µM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.

In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase.

Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15µM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42µM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX.

Synthesis of bis-indolylmethanes as new potential inhibitors of ß-glucuronidase and their molecular docking studies.

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for ß-glucuronidase inhibitory potential. All analogs showed varying degree of ß-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 µM when compared with the standard drug d-saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 µM). Derivatives 1-32 showed the highest ß-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of ß-glucuronidase enzyme. This study has culminated in the identification of a new class of potent ß-glucuronidase inhibitors.