333766-75-9Relevant academic research and scientific papers
Promising bactericidal approach of dihydrazone analogues against bio-film forming Gram-negative bacteria and molecular mechanistic studies
Rakesh,Vivek,Manukumar,Shantharam,Bukhari,Qin, Hua-Li,Sridhara
, p. 5473 - 5483 (2018)
Gram-negative members of the ESCAPE family are more difficult to treat, due to the presence of an additional barrier in the form of a lipopolysaccharide layer and the efficiency of efflux pumps to pump out the drugs from the cytoplasm. The development of alternative therapeutic strategies to tackle ESCAPE Gram-negative members is of extreme necessity to provide a solution to the cause of life-threatening infections. The present investigations demonstrated that compounds 17, 20, 25 and 26 possessing the presence of electron donating (OH and OCH3) groups on the phenyl rings are highly potent; whereas compounds 9, 10, 15, 16, 18, 33 and 36 showed moderate activity against Gram-negative bacteria. An excellent dose-dependent antibacterial activity was established compared to that of the standard antibiotic ampicillin. Significant anti-biofilm properties were measured quantitatively, showing optical density (O.D) values of 0.51 ± 015, 0.63 ± 0.20, 0.38 ± 0.07 and 0.62 ± 0.11 at 492 nm and the leakage of cellular components by the compounds, such as 17, 20, 25 and 26, increased the O.D. of respective treated samples compared to the control. In addition, the implication of experimental results is discussed in the light of the lack of survivability of planktonic bacteria and biofilm destruction in vitro. These results revealed the great significance of the development of a new generation of synthetic materials with greater efficacy in anti-biofilm properties by targeting to lock the bio-film associated protein Bap in Gram-negative bacteria.
Multi-targeted dihydrazones as potent biotherapeutics
Li, Chen,Sridhara,Rakesh,Vivek,Manukumar,Shantharam,Qin, Hua-Li
supporting information, p. 389 - 395 (2018/09/13)
Hydrazone compounds were considered as a useful moiety in drug design development. Therefore, these studies were aimed at the synthesis of new dihydrazones and were screened for their in vitro H+/K+-ATPase and anti-inflammatory activities. The results revealed that compounds 9 (22 ± 0.62 μg/mL), 10 (26 ± 0.91 μg/mL), 15 (24 ± 0.44 μg/mL), 16 (28 ± 0.63 μg/mL), 17 (12 ± 0.38 μg/mL), 18 (14 ± 0.47 μg/mL), 19 (26 ± 0.54 μg/mL), 20 (16 ± 0.41 μg/mL), 25 (06 ± 0.68 μg/mL) and 26 (08 ± 0.43 μg/mL) showed excellent H+/K+-ATPase activity and their IC50 value were lower than the standard drug Omerazole (48 ± 0.12 μg/mL). Compounds 5 (28 ± 0.65 μg/mL), 6 (24 ± 0.61 μg/mL), 7 (28 ± 0.64 μg/mL), 8 (26 ± 0.45 μg/mL), 11 (30 ± 0.74 μg/mL), 12 (28 ± 0.40 μg/mL), 13 (32 ± 0.24 μg/mL), 14 (30 ± 0.55 μg/mL) and 21 (08 ± 0.47 μg/mL), 22 (12 ± 0.47 μg/mL), 23 (10 ± 0.51 μg/mL) and 24 (14 ± 0.84 μg/mL) showed better anti-inflammatory activity compared to standard indomethacin (44 ± 0.15 μg/mL). The structure activity relationship (SAR) showed that, electron donating groups (OH, OCH3) favored the H+/K+-ATPase and antioxidants activity, whereas, electron withdrawing groups (F, Cl, Br and NO2) favored the anti-inflammatory activity. Furthermore, molecular docking study was performed to investigate the binding interactions of the most active analogs with the active site of H+/K+-ATPase enzyme. Compounds 25 (G-score = ?9.063) and 26 (G-score = ?8.977) showed the highest docking G-scores for H+/K+-ATPase inhibition activity.
