121-60-8Relevant articles and documents
Synthesis, characterization, crystal structures and biological screening of 4-amino quinazoline sulfonamide derivatives
Sunil Kumar,Kudva, Jyothi,Lahtinen, Manu,Peuronen, Anssi,Sadashiva, Rajitha,Naral, Damodara
, p. 29 - 36 (2019)
Three quinazolin-4-ylamino derivatives containing phenylbenzenesulfonamides (7a-7c)were synthesized by reacting (E)-N'-(2-cyanophenyl)-N,N-dimethyl formamidine (6)with different 4-amino-N-(phenyl)benzenesulfonamides (4a-4c)and characterized by different techniques such as HRMS, IR, 1H NMR and 13C NMR spectroscopy. The structural properties were further examined by single crystal X-ray diffraction method. The X-ray data shows that compounds 7a and 7c contain two molecules and 7b contains one molecule in the asymmetric unit. Comparison of conformation of two distinct molecules, “A” and “B”, in the asymmetric unit of 7a and 7c were studied with the aid of reported literature. The in vitro antiproliferative activity of the compounds was tested against two breast cancer cell lines (MDA-MB-231 and MCF7). Compound 7b observed as a highest potent candidate against MDA-MB-231with IC50 of 5.44 μg/mL. Antimicrobial activity was also screened against bacterial and fungal strains. Compound 7a with chloro substitution was observed as the most potent candidate against the Gram-negative bacterial strains, whereas the compounds showed no significant activity against the fungal strain.
Design, synthesis and antimicrobial evaluation of novel benzimidazole-incorporated sulfonamide analogues
Zhang, Hui-Zhen,He, Shi-Chao,Peng, Yan-Jun,Zhang, Hai-Juan,Gopala, Lavanya,Tangadanchu, Vijai Kumar Reddy,Gan, Lin-Ling,Zhou, Cheng-He
, p. 165 - 183 (2017)
A novel series of benzimidazole-incorporated sulfonamide analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Compound 5c gave potent activities against Gram-positive bacteria and fungi, and 2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative bacteria. Both of these two active molecules 5c and 5g could effectively intercalate into calf thymus DNA to form compound?DNA complex respectively, which might block DNA replication to exert their powerful antimicrobial activity. Molecular docking experiments suggested that compounds 5c and 5g could insert into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with guanine of DNA. The transportation behavior of these highly active compounds by human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of active compounds with HSA, and which was also confirmed by the full geometry calculation optimizations.
A new, mild preparation of sulfonyl chlorides
Blotny, Grzegorz
, p. 1499 - 1501 (2003)
A new method was developed for the preparation of sulfonyl chlorides from sulfonic acids under neutral conditions using 2,4,6-trichloro-1,3,5-triazine as chlorinating agent.
Unique para-aminobenzenesulfonyl oxadiazoles as novel structural potential membrane active antibacterial agents towards drug-resistant methicillin resistant Staphylococcus aureus
Wang, Juan,Ansari, Mohammad Fawad,Zhou, Cheng-He
, (2021)
A class of structurally unique para-aminobenzenesulfonyl oxadiazoles as new potential antimicrobial agents was designed and synthesized from acetanilide. Some target para-aminobenzenesulfonyl oxadiazoles showed antibacterial potency. Noticeably, hexyl derivative 8b (MIC = 1 μg/mL) was more active than norfloxacin against drug resistant MRSA. Compound 8b was able to disturb the membrane effectively and intercalate into deoxyribonucleic acid (DNA) to form a steady 8b-DNA complex, which might be responsible for bacterial metabolic inactivation. Molecular docking indicated that 8b could interact with DNA topoisomerase IV through noncovalent interactions to form a supramolecular complex and hinder the function of this enzyme. These results indicated that hexyl derivative 8b deserved further investigation as a new lead compound.
Novel Schiff base-bridged multi-component sulfonamide imidazole hybrids as potentially highly selective DNA-targeting membrane active repressors against methicillin-resistant Staphylococcus aureus
Hu, Yuanyuan,Pan, Guangxing,Yang, Zhixiong,Li, Tiejun,Wang, Juan,Ansari, Mohammad Fawad,Hu, Chunfang,Yadav Bheemanaboina, Rammohan R.,Cheng, Yu,Zhou, Chenghe,Zhang, Jiaheng
, (2021)
A new type of Schiff base-bridged multi-component sulfonamide imidazole hybrids with antimicrobial potential was developed. Some target compounds showed significant antibacterial potency. Observably, butylene hybrids 4h exhibited remarkable inhibitory efficacy against clinical MRSA (MIC = 1 μg/mL), but had no significant toxic effect on normal mammalian cells (RAW 264.7). The highly active molecule 4h was revealed by molecular modeling study that it could insert into the base-pairs of DNA hexamer duplex and bind with the ASN-62 residue of human carbonic anhydrase isozyme II through hydrogen bonding. Furthermore, further preliminary antibacterial mechanism experiments confirmed that compound 4h could effectively interfere with MRSA membrane and insert into bacterial DNA isolated from clinical MRSA strains through non-covalent bonding to produce a supramolecular complex, thus exerting its strong antibacterial efficacy by impeding DNA replication. These findings strongly implied that the highly active hybrid 4h could be used as a potential DNA-targeting template for the development of valuable antimicrobial agent.
Ionic liquid mediated stereoselective synthesis of alanine linked hybrid quinazoline-4(3H)-one derivatives perturbing the malarial reductase activity in folate pathway
Patel, Tarosh S.,Bhatt, Jaimin D.,Vanparia, Satish F.,Patel, Urmila H.,Dixit, Ritu B.,Chudasama, Chaitanya J.,Patel, Bhavesh D.,Dixit, Bharat C.
, p. 6635 - 6646 (2017)
Grimmel's method was optimized as well as modified leading to the cyclization and incorporation of alanine linked sulphonamide in 4-quinazolin-(3H)-ones. Further, the generation of heterocyclic motif at position-3 of 4-quinazolinones was explored by synthesis of imines, which unfortunately led to an isomeric mixture of stereoisomers. The hurdle of diastereomers encountered on the path was eminently rectified by development of new rapid and reproducible methodology involving the use of imidazolium based ionic liquid as solvents as well as catalyst for cyclization as well as synthesis of imines in situ at position-3 leading to procurement of single E-isomer as the target hybrid heterocyclic molecules. The purity and presence of single isomer was also confirmed by HPLC and spectroscopic techniques. Further, the synthesized sulphonamide linked 4-quinazolin-(3H)-ones hybrids were screened for their antimalarial potency rendering potent entities (4b, 4c, 4 l, 4 t and 4u). The active hybrids were progressively screened for enzyme inhibitory efficacy against presumed receptor Pf-DHFR and h-DHFR computationally as well as in vitro, proving their potency as dihydrofolate reductase inhibitors. The ADME properties of these active molecules were also predicted to enhance the knowhow of the oral bioavailability, indicating good bioavailability of the active entities.
Design, solvent-free synthesis and antibacterial activity evaluation of new coumarin sulfonamides
Aminarshad, Farzaneh,Heidari, Shima,Mostajeran, Neda,Massah, Ahmad Reza
, p. 547 - 562 (2021/08/16)
A simple cost-effective and green method was presented for the synthesis of coumarin bis sulfonamides. Seventeen novel coumarin sulfonamides were synthesized in good to high yield and purity in six steps starting from 2-amino thiazole, aniline, and 4-methoxy aniline. All of the reactions have been done under green conditions without using any hazardous solvent. The chemical structures of the products were elucidated by IR, 1H NMR, and 13C NMR spectroscopy and elemental analysis. Also, the anti-bacterial properties of the synthesized sulfonamides were investigated using two strains of Staphylococcus (gram-positive) and Escherichia coli (gram-negative) bacteria.
Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
, p. 4567 - 4587 (2021/05/06)
The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation
Manzoor, Shoaib,Prajapati, Santosh Kumar,Majumdar, Shreyasi,Raza, Kausar,Gabr, Moustafa T.,Kumar, Shivani,Pal, Kavita,Rashid, Haroon,Kumar, Suresh,Krishnamurthy, Sairam,Hoda, Nasimul
, (2021/02/16)
Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by 1HNMR, 13CNMR, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC50 = 47.33 ± 0.02 nM and 51.36 ± 0.04 nM and moderate inhibition against BuChE; IC50 = 159.43 ± 0.72 nM and 153.3 ± 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced Aβ1-42 aggregation in thioflavin T-assay at 10 μM and 20 μM, but BS-10 at 10 μM and 20 μM concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced Aβ1-42 aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and Aβ disaggregator for the treatment of AD.