A series of 1,4-bis(decoxyphenyl)carbamothioyl-terephthalamide derivatives was successfully synthesised by reaction of benzene-1,4-dicarbonyl isothiocyanate intermediates with long alkyl chain. The alkylation was performed via Williamson etherification of 4-acetamidophenol with bromoalkanes. The synthesised bis(thiourea) derivatives differed in the chain length, C_nH_2n+1, wheren=10, 12, and 14. The structures of all compounds were characterised by elemental CHN analysis, IR,¹H, and¹³C NMR spectroscopies. Bacteriostatic activities of bis(thiourea derivatives which consisted of two folds of N-H, C=O, and C=S and long alkyl chain substituents were carried out against Gram-negative bacteria (Escherichia coli, ATCC 25922) via turbidimetric kinetic method. Bis(thiourea) derivatives withn=10andn=12displayed excellent activity againstE. coliwith MIC of 135 µg/mL and 145 µg/mL, respectively, while bis(thiourea) derivatives withn=14acted as cutoff point with no antibacterial properties. Similar trend was observed in binding affinity to the active site of enoyl ACP reductase (FabI), which demonstrated binding free energy of-5.3Kcal/mol and-4.9and-4.8 Kcal/mol, respectively.

A new series of aspirin bearing alkylated amines moieties1–12were synthesised by reacting isothiocyanate with a series of aniline derivatives in overall yield of 16–56%. The proposed structures of all the synthesised compounds were confirmed using elemental analysis, FTIR, and¹H and ¹³C NMR spectroscopy. All compounds were evaluated for antibacterial activities againstE. coliandS. aureus viaturbidimetric kinetic and Kirby Bauer disc diffusion method. Compound5bearingmeta-CH₃substituent showed the highest relative inhibition zone diameter against tested bacteria compared toorthoandparasubstituent. Furthermore, aspirin derivatives bearing shorter chains exhibited better bacterial inhibition than longer alkyl chains.

Chemical modification of active scaffolds from natural products has gained interest in pharmaceutical industries. Nevertheless, the metabolites extraction is time-consuming while the lead is frequently mismatched with the receptor. Here, the diazo coupling approach was introduced to generate a series of vanillin derivatives featuring halogenated azo dyes (1a-h). The vanillin derivatives showed effective inhibition of S. aureus (7-9 mm) and E. coli (7-8 mm) compared to the parent vanillin, while 1b had the highest inhibition zone (9 mm) against S. aureus comparable to the reference ampicillin. The presence of N = N, C = O, -OH, -OCH3 and halogens established strategic binding interactions with the receptor. The potential vanillin-azo as an antimicrobial drug was supported by in silico docking with penicillin-binding proteins and DFT (using Gaussian 09) with binding affinity -7.5 kcal/mol and energy gap (Egap) 3.77 eV, respectively. This study represents a significant advancement in drug discovery for effective antibiotics with excellent properties.

In this study, hexasubstituted thiourea was carried out via reaction of isothiocyanato cyclophosphazene intermediates with a series of aromatics amines and amino acids in a one-pot reaction system. The reaction was not as straightforward as typical thiourea synthesis. Six unexpected thiourea derivatives3a–fwere formed in the presence of cyclotriphosphazene moieties in good yields (53–82%). The structures of3a–fwere characterized by elemental analysis and FTIR,¹H,¹³C, and³¹P NMR spectroscopies. The occurrence of reverse thioureas formation in a one-pot reaction system is discussed. The possible binding interaction of the synthesised thiourea3a-bin comparison to the predicted phenyl thiourea5a-band the targeted4awith enzyme enoyl ACP reductase (FabI) is also discussed. Molecular docking of the targeted hexasubstituted thiourea4ais able to give higher binding affinity of −7.5 kcal/mol compared to5a-b(−5.9 kcal/mol and −6.3 kcal/mol) and thiourea3a-b(−4.5 kcal/mol and −4.7 Kcal/mol).

A series of mono-substituted thiourea (2a–i) and bis-substituted thiourea-azo (3a–f) derived from paracetamol derivatives were prepared from isothiocyanates with one and two equivalents of halogenated azo dyes, respectively. The incorporation of azo-derived paracetamol via thiourea moiety in 2a–i depicted excellent microbial activity on Staphylococcus aureus, and 2-(((3-((2-bromophenyl)diazenyl)-4-hydroxyphenyl)carbamothioyl)carbamoyl)phenyl acetate, 2a showed equivalent inhibition properties to the standard ampicillin (10 mm). The structure–activity relationship studies of 2a were supported via molecular docking interaction against S. aureus tyrosyl-tRNA synthetase protein which displayed a free energy interaction of −7.7 kcal/mol compared to aspirin (−6.4 kcal/mol). GRAPHICAL ABSTRACT