James Anayochukwu Ezugwu

A series of novel sulfonamide derivatives ( 4a – i ) was synthesized via a three‐step sequence involving Schiff base formation, sodium borohydride reduction to the corresponding secondary amines ( 2a – i ), and subsequent treatment with p ‐toluenesulfonyl chloride in the presence of sodium carbonate. The structures of all intermediates and final products were unambiguously confirmed by FT‐IR, ¹ H NMR, ¹³ C NMR, and HRMS analyses. The antioxidant activity of the target compounds was assessed using the DPPH radical scavenging assay with BHT as a reference standard. Among the synthesized derivatives, compound 4d exhibited the most pronounced antioxidant activity, surpassing BHT at concentrations of 37.5 and 62.5 µg/mL. The cytotoxicity of the compounds was evaluated against human ovarian carcinoma (A2780) and prostate cancer (LNCaP) cell lines using the MTT assay, with docetaxel as a positive control. Compounds 4g , 4h , and 4i demonstrated the highest cytotoxic potency against both cell lines, with compound 4h displaying a log IC ₅₀ value of 1.343 µg/mL against LNCaP cells. Structure–activity relationship analysis suggests that the methoxy substituent enhances cytotoxic activity, likely through increased lipophilicity and electron‐donating effects facilitating interactions with biological targets. Molecular docking studies were performed to further rationalize the observed biological activities.

A series of nine substituted derivatives of 4‐methyl‐2‐(3‐methyl‐2‐(4‐methylphenylsulfonamido)‐butanamido)thiazole‐5‐carboxylate were synthesized, characterized, and evaluated for antimalarial activity. The synthesis involved a two‐step process using methyl acetoacetate and various substituted benzenesulfonamoyl alkanamides. Structural confirmation was achieved using NMR and mass spectroscopy. The in vivo antimalarial efficacy was tested against Plasmodium berghei in Swiss albino mice, with artemisinin as the reference drug. Compounds 4e and 4h exhibited the highest inhibition rates of 81.68% and 85.34%, respectively, closely matching artemisinin (90%). Structure–activity relationship (SAR) analysis identified the sulfonamide group, alkyl chain length, and molecular flexibility as critical determinants of activity. Docking studies revealed strong binding affinities for 4e and 4h, supported by stable hydrogen bonds and hydrophobic interactions with the enzyme's active site, corroborated by molecular dynamics simulations. ADMET analysis revealed favorable pharmacokinetic and safety profiles, including high GI absorption, acceptable solubility, and low mutagenic risk. These findings highlight compounds 4e and 4h as promising leads for antimalarial drug development.

Five new sulfonamide deriatives bearing dipeptide moieties (4a-e) were synthesized and assessed for their inhibitory activity against acetylcholinesterase and butyrylcholinesterase. First, the condensation reaction of benzenesulfonyl chlorides (1a-c) and various amino acids (2a-d) led to the formation of various amino acid derivatives of sulfonamide (3a-e), which were further treated with amino acids (2a-d), using phenylboronic acid as a catalyst, to obtain the sulfonamide containing dipeptide moiety (4a-e) . The compounds were characterized using ¹ H and ¹³ C NMR spectra. The acetylcholinesterase and butyrylcholinesterase inhibitory studies showed that compounds 4a, 4b, and 4c had high inhibition efficiency at both high and low concentrations of acetylcholinesterase, while compounds 4d and 4e could only inhibit acetylcholinesterase at low concentrations. It also showed that compounds 4a, 4b, 4c, and 4e had high inhibition efficiency at both high and low concentrations of butyrylcholinesterase, while compound 4d could only inhibit butyrylcholinesterase at low concentrations. Their in‐silico physiochemical properties, bioactivity, and drug‐likeness were predicted, while the IC ₅₀ values were reported as mean ± standard deviation from triplicate measurements and compared to the standard drug donepezil. Compound 4a displayed the best activity with IC ₅₀ of 0.89 and 2.74 μM against acetylcholinesterase and butyrylcholinesterase, respectively.

: Carbohydrazides and their Schiff bases are important classes of heterocycles that are not only employed in the area of organic chemistry but also have tremendous applications in physical and inorganic chemistry. A series of potentially bioactive compounds containing carbohydrazide functionality and their hydrazone derivatives have been synthesized and screened for antibacterial, anticancer, antifungal and anti-inflammatory, etc. This brief review discloses some synthetic routes to so many reported carbohydrazides, their Schiff bases, their biological activities, and their structure-activity relationship.

A new series of novel dipeptide sulfonamide analogues were designed, synthesized, and screened for their in silico studies and in vivo antimalarial activities. The synthesized compounds (50 mg/Kg) showed significant activity against P. berghei (NK65) with % inhibition values in (5.9 to 64.7 %) range in when compared with reference drug, artemisinin (66.7 %) in a four day suppressive assay. The in silico studies predicted favorable binding affinity of compounds with target protein residues with high dock score against P. falciparum falcipain 2 (FP‐2) and falcipain 3 (FP‐3) proteins in comparison with the reference ligands. The synthesized compounds showed druggable properties, and the predicted (absorption, distribution, metabolism, excretion and toxicities (ADMET) properties were within the acceptable limits. Molecular dynamics simulation study of the most active compound, 8 e was performed in order to further validate the stability of the protein‐ligand complex and the protein‐ligand interactions.

In the tropics, malaria is among the most serious infectious diseases in developing countries. The discovery of the artemesinin antimalarial drug not too long ago was a major breakthrough in the effort to combat the malaria disease. However, recent reports of resistance even to combination therapy involving artemisinin are very worrisome and have led to the search for new chemical agents to sustain the fight against malaria. The carboxamide functionality has been shown to be an important pharmacophore in over 25% of commercial chemotherapeutic agents. Three benzensulphonamides (3a–c) were prepared from the reaction of the appropriate benzensulphonyl chloride (1a–c) and alanine (2) in aqueous basic medium. Eight tert-butylamino-oxo-ethylcarbamates (5a–h) were also prepared from reacting commercially available boc-glycine (4) and different amines using peptide coupling reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt), with triethyl amine and dichloromethane (DCM) as solvents. The target compounds were prepared by reacting compounds 3a–c with compounds 5a–h in the presence of coupling reagents to get twenty four (24) different compounds. The compounds were characterized and evaluated for their antiplasmodial activity. Computed molecular descriptors and assessed biochemical parameters showed that the compounds were drug-like and safe. All the compounds had favourable binding interactions with residues at the PABA binding site of homologically modeled P. falciparum dihydropteroate synthase and henceforward the in vitro and in vivo antiplasmodial activities were evaluated. Compounds 7a–7x showed activity against P. falciparum (W2 strain) at MIC values ranging from 3.52 to 0.09 μM. Moreover, seven of the compounds (7c, 7d, 7i, 7j, 7p, 7r and 7s) showed better activity than quinine (MIC = 0.72 μM). In addition, 16 of the 24 compounds were found to clear more than 50 percent of P. berghei (NK-65 strain) from the blood of infected mice at 12 days post-infection. The percentages of parasites cleared by 20 mg kg⁻¹ of the three most effective compounds (7g, 7n and 7r) were 74.98, 74.98 and 74.07, respectively. In conclusion, 7r (MIC 0.71 μM) from this class of glycine derived sulfonamides has the ability to clear 74.07% of P. berghei from blood of infected mice at 20 mg kg⁻¹ and an interesting pharmacokinetic profile (M_W = 430.31 Da, HBA = 7, HBD = 3, log P = 2.56, NRB = 9 and TPSA = 104.37 Ų), which is in agreement with the Lipinski rule of 5 for a compound to be qualified as a drug candidate. 7r could serve as a lead in developing new antiplasmodial agents.