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Synthesis and Biological Evaluation of New Tetra‐aza Macrocyclic Scaffold Constrained Oxadiazole, Thiadiazole and Triazole Rings
Author(s) -
Vinay Kumar B.,
Naik H. S. Bhojya,
Girija D.,
Sharath N.,
Sudeep H. V.,
Joy Hoskeri H.
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100181
Subject(s) - chemistry , acetamide , benzene , dpph , acetanilide , triazole , 1,2,4 triazole , medicinal chemistry , stereochemistry , tetra , oxadiazole , antioxidant , organic chemistry
A new series of N,N ′‐(benzene‐1,3‐diyldi‐1,3,4‐oxadiazole‐5,2‐diyl)bis{2‐[(5‐benzene‐1,3‐diyl‐1,3,4‐oxadiazol‐2‐yl)amino]acetamide}(macrocycle 1 ) , N,N ′‐(benzene‐1,3‐diyldi‐1,3,4‐thiadiazole‐5,2‐diyl)bis{2‐[(5‐benzene‐1,3‐diyl‐1,3,4‐thiadiazol‐2‐yl)amino]acetamide} (macrocycle 2 ) and S,S ′‐[benzene‐1,3‐diylbis(4H‐1,2,4‐triazole‐5,3‐diyl)]bis{[(5‐benzene‐1,3‐diyl‐4H‐1,2,4‐triazol‐3‐yl)sulfanyl]ethanethioate}(macrocycle 3 ) was synthesized from isophthalic dihydrazide ( 4 ) through a multistep reaction sequence. All the synthesized compounds were screened for their inhibitory effect against four different bacterial strains: P. aeruginosa ATCC‐20852, K. pneumoniae MTCC‐618, S. aureus ATCC‐ 29737, S. typhi MTCC‐ 3214. The synthesized compounds showed a significant zone of inhibition and the results were comparable with that of the standard drug ciprofloxacin. The synthesized compounds were further studied for their possible in vitro antioxidant effects by DPPH scavenging, total antioxidant capacity, total reductive capacity and H 2 O 2 scavenging activity. The results indicated that the in vitro antioxidant activity for all the three molecules was efficient when compared to the standards. The DNA interaction behavior of macrocycles 1–3 with CT‐DNA was investigated by the absorption spectra obtained (K b constant for 1 is 4.53 × 10 4 M −1 , for 2 is 5.75 × 10 4 M −1 and for 3 is 5.86 × 10 4 M −1 ). Based on the results it can be interpreted that the reducing power effect of the newly synthesized compounds demonstrates a direct effect on DNA binding and hence inhibiting the bacterial growth through their action on DNA by inhibiting DNA replication or DNA transcription.