Alkylpyrimidine derivatives, particularly thiopental-based analogs, have emerged as promising scaffolds for antimicrobial drug development. In this study, we designed and synthesized a series of novel thiopental-pyrimidine hybrids (3a–c, 4) through efficient condensation reactions, and characterized these compounds by using NMR, IR, and mass spectrometry. Antimicrobial screening revealed significant activity against clinically relevant strains: derivative 3a exhibited selective inhibition of Bacillus subtilis (MIC: 10.5±0.4 mg/mL) and Escherichia coli (MIC: 22.1±0.3 mg/mL), while 3c showed potent antifungal effects against Candida albicans (MIC: 11.6±0.4 mg/mL). Molecular docking studies elucidated the mechanistic basis of this activity, with 3a binding to penicillin-binding protein (PBP; −6.4 kcal/mol) via hydrogen bonds (SER392) and hydrophobic interactions (TYR430, PRO660), and 3c coordinating with the heme iron of CYP51 (−7.8 kcal/mol) akin to fluconazole. Notably, 3c thioether linkage facilitated π-cation/anion interactions with PHE463, rationalizing its antifungal specificity. Structure-activity relationships (SAR) underscored the critical roles of electron-deficient pyrimidine cores for antibacterial activity and sulfur moieties for antifungal action. These findings position thiopental-pyrimidine hybrids as versatile leads for combating microbial resistance, with 3c representing a particularly promising antifungal candidate. Our integrated synthetic, biological, and computational approach provides a blueprint for optimizing these scaffolds for clinical translation.

The development of effective insecticides is crucial for sustainable agriculture. This research focuses on a series of pyridine derivatives (3–9) that were prepared and evaluated for their agricultural bioefficacy as potential insecticides against cowpea aphid, Aphis craccivora Koch (Homoptera: Aphididae). The results demonstrate significant variations in bioefficacy among the tested compounds. Toxicity index analysis revealed the following order of insecticidal activity: 8>4>6>3>5>7>9, highlighting compound 8 as the most potent. Furthermore, potential binding interactions were elucidated through molecular docking studies between these compounds and relevant insect target proteins. So, the observed bioactivity trends were rationalized with the use of the docking data, which offered useful information on the binding affinities and molecular interactions. AChE, or acetylcholine esterase (PDB ID: 2ACE), has been docked against the seven synthetic molecules (3–9). Interestingly, compounds (2-(pyridin-2-ylthio)acetonitrile; 8), (2-(pyridin-2-ylthio)acetic acid; 6), and (ethyl 2-(pyridin-2-ylthio)acetate; 4) had the highest binding affinity, with respective docking scores (S) of -7.51, -7.45, and -7.12 kcal/mol, while compounds (thieno[2,3-b]pyridine derivatives; 7 and 9) had the lowest binding affinity (S=-6.52 and -6.73 kcal/mol, respectively). According to protein-ligand docking configurations, these compounds exhibited a range of binding interactions inside the 2ACE active site. Hence, this study contributes to the development of new pyridine-based insecticides for sustainable pest management in agricultural applications.

In examining for unique insecticidal agents, two derivatives namely, 2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)-N-(4-nitrophenyl)acetamide (2) and 3-amino-N-(4-nitrophenyl)-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (3) were synthesized from distyrylpyridine-2-thione (1). The new compounds were structurally clarified by spectral and elemental analysis data. The insecticidal activity of these compounds were carried out against cowpea aphid, Aphis craccivora Koch. It is demonstrated that the compounds 2 and 3 have noteworthy insecticidal activity against nymphs of cowpea aphid with LC50 values of 0.025-0.027 ppm and 0.005-0.006 ppm after 24 h and 48 h of treatment, respectively. Also, the compounds 2 and 3 have noteworthy insecticidal activity against adults of cowpea aphid with LC50 values of 0.112-0.129 ppm and 0.014-0.015 ppm after 24 h and 48 h of treatment, respectively, that were comparable to that of the control acetamiprid.

Oxygen-containing heterocycles are largely distributed in natural and synthetic compounds. Coumarins are among the most famous heterocycles which possess one oxygen atom in their rings. Coumarins are classified as multifunctional scaffold and are used as anti-oxidant reagents, anti-inflammatory, anti-microbial, anti-fungal, anti-HIV active, analgesic, anti-histaminic, insecticides, dyes, herbicides, sensitizers, perfumes, cosmetics and food additives. Due to their diverse applications in industrial and pharmaceutical fields, many chemists have given significant interest to these compounds. Herein, the review highlights various methods for the synthesis and interactions of coumarin moiety as one of the most efficient categories of heterocycles.

Pyrimidine compounds continue to attract great interest in the field of organic synthesis due to their various chemical and biological applications observed, especially in recent times. As a result, this review covering some periods from 1957 to 2021 has been prepared to discuss some of the structural pathways of these compounds as well as some of their interactions and applications.

Thiazolopyrimidnes are considered one of the most interesting classes in heterocyclic chemistry due to their pharmaceutical importance. Herein, we report the synthesis of some new heterocyclic compounds containing thiazolopyrimidine starting from compound (1) which was previously prepared in literature. The starting compound was allowed to react with different alkylating agents such as chloroacetone, chloroacetyl chloride, and phenacyl bromide to afford derivatives (2-4). Compound (5), benzylidene derivative, was obtained by the reaction of compound (2) with benzaldehyde while amino-dicarbonitrile compound (6) can be obtained by the reaction of compound (5) and malononitrile. Acetylation of amino group in compound (6) with chloroacetyl chloride led to formation of compound (7). Nucleophilic substitution of chlorine in compound (7) by aniline gave compound (8) which further subjected the Munich reaction to form compound (9). All new synthesized compounds were characterized using different elemental and spectral analysis.

Starting from 3-cyano-4,6-distyrylpyridin-2(1H)-thione (1), the compound N-(4-chlorophenyl)-2-((3-cyano-4,6-distyrylpyridin-2-yl)thio)acetamide (2) was prepared. Compound (2) underwent cyclization upon heating in ethanolic sodium ethoxide solution to give the corresponding cyclized form 3-amino-N-(4-chlorophenyl)-4,6-distyrylthieno[2,3-b]pyridine-2-carboxamide (3). The elemental analyses and spectroscopic data of compounds (2) and (3) are in agreement with their proposed structures. Their insecticidal activity against cowpea aphid, Aphis craccivora Koch, was studied. The results of insecticidal activity for compounds (2) and (3) against the nymphs and the adults of the tested insects exhibited that compounds (2) and (3) have a higher insecticidal activity than that of acetamiprid, a reference insecticide, after 24 h of treatment.