Combined drug design of potential Mycobacterium tuberculosis and HIV-1 inhibitors: 3’,4’-di-substituted -4'H-spiro[isothiochromene-3,5'-isoxazol]-4(1H)-one

Abstract

We report herein the design and synthesis of 17 new spiroheterocycles 10-26, on the basis of two hypothetical pharmacophore structures designed to interact with both of Mycobacterium tuberculosis bacteria and HIV-1 virus. The in vitro biological evaluation of these compounds allowed us to point out seven new potential non-nucleoside hits, with MIC values in the range of 6.25 µg/mL and two new potential anti-HIV-1 inhibitors .

Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site

“…It was believed that amide can exist in two major tautomeric forms, keto-amine and hydroxy-enamine, although keto-amine form is predominant in the solid state [ 28 ] as shown in Figure 1 . We investigated the potential pharmacophores of various bioactive compounds for their antibacterial [ 29 – 33 ], antifungal [ 34 , 35 ] and antiviral activity [ 36 ], and verified them further with Petra/Osiris/Molinspiration (POM) analyses. On the basis of our previously published findings in antibacterial, antiviral and antifungal fields, we can safely conclude that our present series, ABD 1 – 10 , also contain a pharmacophore responsible for antifungal and antibacterial activities which is elaborated in Figure 2 .…”

Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study

“…Tautomerism in bioactive compounds plays a key role in the orientation of bioactivity of drugs that have found wide application in drug design, ranging from new medicinal materials to antibacterial imidazo[1,2-a]pyrimidine (-pyridine), 46 as sulphonamides in the antifungal agents 47 and as potential antiHIV spiroheterocycles. 48 Similar to HPMBP, compound 6 is also likely to exist as four tautomers (Scheme 3) in water, although it exists as tautomer 6c in the solid state. To understand the inhibitory mechanism and acting sites of compound 6 to 20S proteasome, knowing which tautomer actually exists in the solution environment is indispensable.…”

Computational POM and DFT Evaluation of Experimental in-vitro Cancer Inhibition of Staurosporine-Ruthenium(II) Complexes: The Power Force of Organometallics in Drug Design

“…A suitable theoretical concept is that proposed by Ben Hadda et al [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] apropos of definition of pharmacophore site. The best descriptors for studying and identifying the type of pharmacophore site (antibacterial, antiviral or antitumor) are the description in detail of local electrophilicity and the nucleophilicity of each functionalized group and their spatial arrangement.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22] Recently, it has been shown that the kinase inhibition by an organometallic systems under biological condition may be significantly facilitated if a ligand containing an anti-kinase pharmacophore (NH-C=O), a bidentate N,N coordinative site (staurosporine derivatives) and non-toxic metal (ruthenium) are available. [2][3][4][5][6] The cancer inhibition of kinase enzymes through organic drugs has been the subject of different theoretical investigations.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] For these reasons, we constructed a platform of some of the key bioinformatic model in order to predict and characterize the antitumor drugs performance of the tested series of staurosporine-ruthenium(II) complexes. Our aim in this work is to give a deeper insight into the coordination effect of transition metal (ruthenium) to bioactive drug (staurosporine), on the inhibition efficiency of ruthenium-staurosporine complexes ( Figure 1) using POM and DFT analyses.…”