173538-48-2Relevant academic research and scientific papers
Structural comparison of Mtb-DHFR and h-DHFR for design, synthesis and evaluation of selective non-pteridine analogues as antitubercular agents
Sharma, Kalicharan,Tanwar, Omprakash,Sharma, Shweta,Ali, Shakir,Alam,Zaman,Akhter, Mymoona
, p. 319 - 333 (2018)
Tuberculosis is an infectious disease that affects millions of population every year. Mtb-DHFR is a validated target that is vital for nucleic acids biosynthesis and therefore DNA formation and cell replication. This paper report identification and synthesis of novel compounds for selective inhibition of Mtb-DHFR and unleash the selective structural features necessary to inhibit the same. Virtual screening of databases was carried out to identify novel compounds on the basis of difference between the binding pockets of the two proteins. Consensus docking was performed to improve upon the results and best ten hits were selected. Hit 1 was subjected to analogues design and the analogues were docked against Mtb-DHFR. From the docking results 11 compounds were selected for synthesis and biological assay against H37Rv. Most potent compound (IND-07) was tested for selectivity using enzymatic assay against Mtb-DHFR and h-DHFR. The compounds were found to have good inhibitory activity (25–200 μM) against H37Rv and in enzyme assay against Mtb-DHFR and h-DHFR the compound was found selective towards Mtb-DHFR with selectivity index of 6.53. This work helped to identify indole moiety as novel scaffold for development of novel selective Mtb-DHFR inhibitors as antimycobacterial agents.
CHEMOSELECTIVITY OF INDOLE DICARBOXYLATE TOWARDS HYDRAZINE HYDRATE: SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF OXADIAZOLYL/PYRROLYL/TRIAZOLYL/PYRAZOLYLMETHOXYINDOLE DERIVATIVES
Gadaginamath, Guru S.,Joshi, Raghavendra G.,Kamat, Anand G.
, p. 475 - 484 (2007/10/02)
The exclusive formation of substituted indol-5-yloxyacid hydrazides (4a-h) from 3-carbethoxy-5-ethoxy-carbonylmethoxyindoles (2a-h) revealed the chemoselectivity of C-5 ester over C-3 carboxy ester function towards the nucleophilic attack of hydrazine hydrate.These hydrazides (4a-h) were treated separastely with triethyl-orthoformate, carbon disulphide and ethanolic potassium hydroxide followed by treatment with hydrazine hydrate (99percent), acetonyl, acetone and acetyl acetone to furnish the desired substituted 5-(1', 3', 4'-oxadiazol-2'-yl)-methoxyindoles (5a-h), 5-(4'-amino-5'-mercapto-1'-2', 3'-triazol-3'-yl) methoxyindoles doles (6a-h), 5'-(2', 5'-dimethyl-pyrrol-1'-yl) aminocarbonylmethoxyindoles (7a-h) and 5-(3', 5'-dimethlpyrazol-1'-yl) carbonylmethoxyindoles (8a-h), respectively.The Schiff base of hydrazide (9d) obtained from hydrazide (4d) and ethyl acetoacetate on heating with o-dichlorobenzene furnished dimer (11d) instead of pyrazolonylindole (10d).The newly synthesised compounds were screened for their antibacterial and antifungal activities.
