Nano silver particles catalyzed synthesis, molecular docking and bioactivity of α-thiazolyl aminomethylene bisphosphonates

Abstract

A new series of α-thiazolyl aminomethylene bisphosphonates were synthesized by a three component reaction of 4-aryl substituted thiazol-2-amine with different dialkyl/aryl phosphites and triethyl orthoformate in the presence of Ag NPs (nano particles) as a catalyst under solvent free conditions. All the synthesized target compounds were characterized by ¹H, ¹³C, ³¹P, mass and elemental analysis. The target compounds were screened for their in vitro antioxidant, antibacterial and antifungal activity. Molecular docking studies were also performed. The results revealed that among the synthesized compounds tetramethyl(((4-(4-methoxyphenyl)thiazol-2-yl)amino) methylene)bis(phosphonate) (5d), tetramethyl(((4-(4-fluorophenyl)thiazol-2-yl)amino) methylene) bis(phosphonate) (5h), and tetramethyl(((4-(4-bromophenyl)thiazol-2-yl)amino)methylene) bis (phosphonate) (5j) showed remarkably higher antioxidant activity by DPPH and H₂O₂ than the standard ascorbic acid. Compounds tetramethyl(((4-phenyl thiazol-2-yl)amino) methylene) bis(phosphonate) (5a), 5d, 5h and tetraethyl(((4-(4-bromophenyl)thiazol-2-yl) amino)methylene)bis (phosphonate) (5k) showed good antibacterial activity. 5a, 5d, and 5h also showed rather higher antifungal activity than the standard flucanozole. Computational docking methods have been used to predict how several aminomethylene bisphosphonate derivatives compete against the inhibitor BPH-1330 at the crystal enzyme structure of the 4H3A protein active site and how R and R₁ influence their binding ability.

Graphical Abstract

Keywords:

• α-Thiazolyl aminomethylenebisphosphonates
• nano Ag particles
• antioxidant
• antibacterial
• antifungal
• docking studies

Acknowledgments

The authors are thankful to Prof. C. Devendranath Reddy, Department of Chemistry, S.V. University, Tirupati for his helpful discussions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

One of our authors Mr. Mohan Gundluru expresses sincere thanks to the funding DST-PURSE 2nd Phase Program in S.V. University, Tirupati funded by DST-New Delhi, India for providing instrumentation facility through SRF (File No: 17118-UGC-III(3)/DST-PURSE 2nd Phase/2017, Dt: 23-08-2018).