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A series of 2,4-dichloro-5-{[4-(phenylsulfonyl)piperazin-1-yl]carbonyl}benzenesulfonamides were designed and synthesized through amidation of Lasamide 1 with substituted piperazines. The newly obtained compounds demonstrated remarkable inhibition potency and selectivity for the human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) II isoform. Selected compounds 7 and 9 were investigated in an in vivo model of glaucoma and showed relevant performances, with the latter being able to last the effect up to 4 hours. The results herein reported are in sustainment of Lasamide derivatives as a new class of compounds potentially exploitable for the management of uncontrolled intra ocular pressure (IOP)., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Lasamide is a synthetic precursor and a contaminant of the diuretic Furosemide manufacturing process and represents a highly valuable building block for fragment-based drug discovery approaches. We assessed the ability of Lasamide to inhibit in vitro the human-expressed Carbonic Anhydrases by means of the stopped-flow technique, and we assessed its binding modes within hCAs II and XII-mimic catalytic clefts by X-ray crystallography. Interestingly, an unprecedented crystal form for the hCA IX mimic H-tag is reported and discussed herein., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

In this study, a focused library of oxime ester derivatives of 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I and II, as well as the transmembrane and tumor-associated IX and XII isoforms. As a result, we obtained a first line of knowledge on lasamide derivatives potentially useful for development as CA inhibitors (CAIs). In particular, we focused our attention on the derivative 11 , which was selective toward hCAs IX and XII over the cytosolic isoenzymes. An in silico study was conducted to assess the binding mode of 11 within hCAs IX and XII. Also, antiproliferative assays highlighted promising derivatives. The data obtained in this study are currently in use for the development of better-performing compounds on the tumor-associated isoforms., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Objective: The research work aims to synthesize novel series of hydrazones and antioxidant screening. It also aims to evaluate the binding affinities and in silico methods for identifying possible drug targets of synthesized compounds., Methods: This report briefly explains the synthesis of a novel series of hydrazones. It was synthesized via. hydrazinolysis of esters to obtain hydrazide, treated with aldehyde and acetophenone to get hydrazones. The spectral confirmed hydrazones exhibited excellent to comparable anti-oxidant as compared to the standard drugs Butylated hydroxytoluene (BHT) and Ascorbic acid. Molecular docking on myeloperoxidase (MPO) demonstrated the ability of this scaffold to correctly recognize the target and engage in significant bonded and non-bonded interactions with key residues therein., Results and Discussion: In this study, we report effectively synthesized compounds BK-35, BK- 41, BK-26, BK-28, and BK-39 that showed the best DPPH radical scavenging activity. The docking results clearly showed the binding mode of hydrazones into the active site of Myeloperoxidase (MPO). In in-silico results, none of the synthesized compounds, BK-24 to BK- 41, violated Lipinski's rule of five (miLog P ≤ 5)., Conclusions: In vitro preliminary anti-oxidant screening results in support by in Silico binding affinity data of novel hydrazones of levofloxacin related molecules BK-24 to BK-41 reported here have emerged as excellent anti-oxidant agents. The inference derived from the in vitro anti-oxidant screening data and the quantitative insights derived from the per-residue interaction analysis with MPO enzyme are now being fruitfully utilized for site-specific mutation around the nucleus to identify selective and potent anti-oxidants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Levonadifloxacin (WCK 771) is a novel broad-spectrum anti-methicillin-resistant Staphylococcus aureus (MRSA) agent recently launched in India. Five process impurities and one degradation impurity were synthesized as reference standards for their quantification by high-performance liquid chromatography (HPLC) methodology in drug substance and drug product. These compounds are not easily commercially available. The synthesis and characterization of these impurities are discussed in detail., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)