Design,Synthesis, Docking Study of Pyrazolohydrazinopyrimidin-4-one Derivatives and Their Application as Antimicrobials

New series of pyrazoles 4a – c and pyrazolopyrimidines 5a – f had been constructed. The newly synthesized compounds were assessed for their antimicrobial activity towards E. coli and P. aeruginosa (gram –ve bacteria), B. subtilis and S. aureus (gram +ve bacteria) and A. flavus and C. albicans (representative of fungi). The pyrazolylpyrimidine-2,4-dione derivative 5b is the most active candidate against B. subtilis (MIC=60 μg/mL) and P. aeruginosa (MIC=45 μg/mL). Regarding antifungal potential, compound 5f was the most effective against A. flavus (MIC=33 μg/mL). Similarly, compound 5c displayed strong antifungal activity towards C. Albicans (MIC=36 μg/mL) in reference to amphotericin B (MIC=60 μg/mL). Finally, the novel compounds had been docked inside dihydropteroate synthase (DHPS) to suggest the binding mode of these compounds.     

新型2-喹诺酮类Polo样激酶1抑制剂的设计合成及分子对接研究

目的:设计合成新型2-喹诺酮类Polo样激酶1(Plk1)抑制剂。方法:以Plk1抑制剂ON 01910为先导化合物,利用生物电子等排原理设计一系列2-喹诺酮类衍生物,用Autodock软件将该类化合物与Plk1进行分子对接和虚拟筛选,计算结合自由能;以取代的氯(溴)苄为起始原料,先后经巯基乙酸取代、双氧水氧化、与(对甲氧基)苯胺酰化,再经环合、水解制得目标化合物。结果:设计的化合物大多数与Plk1的结合自由能均比ON 01910的低,结合强度高、稳定性好;合成了16个2-喹诺酮类衍生物,产物结构经1H-NMR确证。结论:所得化合物中有15个为新化合物,化合物的结构设计科学合理,虚拟筛选结果良好,为后续实体筛选和化合物结构优化提供了理论依据和参考。     

Design,Synthesis, and Biological Evaluation of Dexibuprofen Derivatives as Novel Anti-Inflammatory,Antioxidant and Molecular Docking Studies

Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC₅₀=19.8 μM), DR9 (IC₅₀=24.8 μM) and DR3 (IC₅₀=47.2 μM) as compared with Dexibuprofen (IC₅₀=156.6 μM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %).     

Design,Synthesis, Insecticidal Activities and Molecular Docking of Sulfonamide Derivatives Containing Propargyloxy or Pyridine Groups

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC₅₀) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC₅₀=18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.     

Design,Synthesis and Molecular Docking Studies of Some Tetrahydropyrimidine Derivatives as Possible Fascin Inhibitors

Eight derivatives of tetrahydropyrimidine scaffold were designed and prepared as hybrid compounds possessing the structural features of both monastrol as an anticancer drug and nifedipine as a fascin blocking agent. All of the compounds were evaluated for their cytotoxic potency and the ability to inhibit 4T1 breast cancer cells migration. Then, they were investigated in silico for their ability to inhibit the fascin protein using molecular docking simulation. The most potent compound was 4d and the weakest one was 4a according to the in vitro cytotoxicity assay. The corresponding IC₅₀ values were 193.70 and 248.75 μm , respectively. The least cytotoxic compound ( 4a ) was one of the strongest ones in binding to the fascin binding site according to the molecular docking results. 4a and 4e inhibited the 4T1 cells migration better than other compounds. They were more potent than nifedipine in inhibiting the migration process. In silico studies proved 4h to be the most potent fascin inhibitor in terms of ΔG_bind although it was not inhibiting migration. The controversy between the in vitro and in silico results may cancel the theory of the involvement of the fascin inhibition in the migration inhibition. However, the considerable antimigratory effects of some of the synthesized compounds encourage performing further in vivo experiments to introduce novel tumor metastasis inhibitors.     

Synthesis,Biological Evaluation,and Docking Study of Ring-Opening Amide Analogs of Matrine as Antitumor Agents

In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo.     

Design,Synthesis, and Biological Evaluation of Novel Indanone Derivatives as Cholinesterase Inhibitors for Potential Use in Alzheimer's Disease

Indanone derivatives containing meta/para-substituted aminopropoxy benzyl/benzylidene moieties were designed based on the structures of donepezil and ebselen analogs as the cholinesterase inhibitors. The designed compounds were synthesized and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were measured. Inhibitory potencies (IC₅₀ values) for the synthesized compounds ranged from 0.12 to 11.92 μM and 0.04 to 24.36 μM against AChE and BChE, respectively. Compound 5 c showed the highest AChE inhibitory potency with IC₅₀ value of 0.12 μM, whereas the highest BChE inhibition was achieved by structure 7 b (IC₅₀=0.04 μM). Structure-activity relationship (SAR) analysis revealed that there is no significant difference between meta and para-substituted derivatives in AChE and BChE inhibition. However, the most potent AChE inhibitor 5 c belongs to meta-substituted compounds, while the most active BChE inhibitor is para-substituted derivative 7 b . The order of enzyme inhibition potency based on the substituted amine group is dimethyl amine>piperidine>morpholine. Compounds containing C=C linkage are more potent AChE inhibitors than the corresponding saturated structures. Molecular docking studies indicated that 5 c interacts with AChE in a very similar way to that observed experimentally for donepezil. The introduced indanone-aminopropoxy benzylidenes could be used in drug-discovery against Alzheimer's disease.     

Synthesis,Antiproliferative Evaluation,and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused Thiazole-Amide Derivatives

Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a – 6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC₅₀ in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC₅₀ against SKOV-3, 13.68 μM IC₅₀ against HepG2, 15.69 μM IC₅₀ against A549, 19.13 μM IC₅₀ against MCF-7, and 22.05 μM IC₅₀ against T-24, showing better and broad-spectrum antiproliferative effect than that of the positive control 5-FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure-activity relationships were found and discussed herein by DFT theoretical calculation.     

Hybrid Pharmacophore Design,Molecular Docking,Synthesis, and Biological Evaluation of Novel Aldimine‐Type Schiff Base Derivatives as Tubulin Polymerization Inhibitor

A series of hybrid aldimine‐type Schiff base derivatives including trimethoxyphenyl ring and 1,2,4‐triazole‐3‐thiol/thione were designed as tubulin inhibitors. The molecular docking simulations on tubulin complex (PDB: 1SA0) revealed that derivatives with nitro and/or chloro or dimethylamino substitutes (4‐nitro, 2‐nitro, 3‐nitro, 4‐Cl‐3‐nitro, and 4‐Me₂N) on the aldehyde ring were the best compounds with remarkable binding energies (?9.09, ?9.07, ?8.63, ?8.11, and ?8.07 kcal mol^?1, respectively) compared to colchicine (?8.12 kcal mol^?1). These compounds were also showed remarkable binding energies from ?10.66 to ?9.79 and ?10.12 to ?8.95 kcal mol^?1 on human (PDB: 1PD8) and Candida albicans (PDB: 3QLS) DHFR, respectively. The obtained results of cytotoxic activities against HT1080, HepG2, HT29, MCF‐7, and A549 cancer cell lines indicated that 4‐nitro and 2‐nitro substituted compounds were the most effective agents by mean IC₅₀ values of 11.84 ± 1.01 and 19.92 ± 1.36 μm , respectively. 4‐Nitro substituted compound (5 μm ) and 2‐nitro substituted compound (30 μm ) were able to strongly inhibit the tubulin polymerization compared to colchicine (5 μm ) and 4‐nitro substituted compound displayed IC₅₀ values of 0.16 ± 0.01 μm compared to that of colchicine (0.19 ± 0.01 μm ). This compound also showed the lowest MIC values on all tested microbial strains including three Gram‐positive, four Gram‐negative, and three yeast pathogens.     

Design,Synthesis and Cytotoxicity of New Coumarin-1,2,3-triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies

A library of new coumarin-1,2,3-triazole hybrids 7a – l were synthesized from 4-(diethylamino)-2-hydroxybenzaldehyde precursor through a series of reactions including Vilsmeier-Haack reaction and condensation reaction to achieve key intermediate oxime and further performed click reaction by using different aromatic azides. We screened all molecules in silico against crystal structure of Serine/threonine-protein kinase 24 (MST3), based on these results all molecules were screened for their cytotoxicity against human breast cancer MCF-7 and lung cancer A-549 cell lines. Compound 7 b (p-bromo) showed best activity against both cell lines MCF-7 and A-549 with IC₅₀ value of 29.32 and 21.03 μM, respectively, in comparison to Doxorubicin corresponding IC₅₀ value of 28.76 and 20.82 μM. Another compound 7 f (o-methoxy) also indicated good activity against both cell lines with IC₅₀ value of 29.26 and 22.41 μM. The toxicity of all compounds tested against normal HEK-293 cell lines have not shown any adverse effects.     

Design,Synthesis, Molecular Docking,and Molecular Dynamics Simulation Studies of Novel 3-Hydroxypyridine-4-one Derivatives as Potential Acetylcholinesterase Inhibitors

Researchers have focused on inhibiting acetylcholinesterase for Alzheimer's disease treatment. In this study, some novel AChE inhibitors were synthesized using hydroxypyridin-4-one plus benzylpiperidine scaffolds which were evaluated using Ellman's method. Accordingly, ((1-(4-methoxyphenethyl)piperidin-4-yl)amino)methyl)-5-hydroxy-1-methylpyridin-4(1H)-one (VII_d) showed weaker but promising AChE inhibition compared to donepezil (IC₅₀=143.090 nM). The average RMSD values of VII_d was found to be 2.25 indicated less structural changes in the active site residues. The phenyl group of the phenyl-ethyl-N-piperidine moiety of VII_d formed hydrophobic interactions with Trp285 and Tyr340. There was a π-cation interaction between nitrogen atom of piperidine ring and Phe294. Another π-cation interaction was found between type 2 amine of linker and Trp85. Piperidine ring interacted with Tyr336, Tyr123, and Phe337 through hydrophobic interactions. Indeed, the VII_d was predicted to be absorbed across the gastrointestinal tract, though it may be pumped out by P-gp. Indeed, VIId can permeate through the blood brain barrier. MD simulation studies revealed that benzyloxy moiety plays a role similar to benzylpiperidine moiety of donepezil in binding to the active site residues. Also, carbonyl group functioned similar to indanone ketone group. Overall; further research on VII_d may lead to introduction of a novel class of AChE inhibitors.     

Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Design,Synthesis, Cytotoxic Screening and Molecular Docking Studies of Novel Hybrid Thiosemicarbazone Derivatives as Anticancer Agents

Thiosemicarbazones have been the focus of scientists owing to their broad clinical anticancer range. Herein, A Series of new thiosemicarbazone derivatives 5 – 9 were synthesized and confirmed through the use of different spectroscopic techniques along with elemental analysis. The in vitro cytotoxic activity of compounds 5 – 9 against MCF-7 and A549 cell lines and normal breast cells were assessed. Several compounds were found to be active. The most active compound 7 caused MCF-7 cell cycle arrest at G1/ S phases; and induced apoptosis at the pre-G1 phase. The apoptosis-inducing activity of compound 7 was proofed by the elevation of caspase 3/7 activity and also by up-regulation of the expression of Bax and p53 proteins together with the down-regulation of the expression of the Bcl-2 protein. It also had a strong inhibitory effect topoisomerase IIβ enzyme. Molecular Docking study revealed that the synthesized compounds had good docking scores compared to the standard drug Etoposide towards the topoisomerase IIβ protein (3QX3). Overall, these findings confirmed that the new thiosemicarbazone derivatives could aid in the development of promising cancer drug candidates.     

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis,Crystal Structure,Molecular Docking and Their Biological Activities

Here, we report the synthesis and characterization of four new aroyl‐hydrazone derivatives L₁ – L₄ , and their structural as well as biological activities have been explored. In addition to docking with bovine serum albumin (BSA) and duplex DNA, the experimental results demonstrate the effective binding of L₁ – L₄ with BSA protein and calf thymus DNA (ct‐DNA) which is in agreement with the docking results. Further biological activities of L₁ – L₄ have been examined through molecular docking with different proteins which are involved in the propagation of viral or cancer diseases. L₁ shows best binding affinity with influenza A virus polymerase PB2 subunit (2VY7) with binding energy ?11.42 kcal/mol and inhibition constant 4.23 nm , whereas L₂ strongly bind with the hepatitis C virus NS5B polymerase (2WCX) with binding energy ?10.47 kcal/mol and inhibition constant 21.06 nm . Ligand L₃ binds strongly with TGF‐beta receptor 1 (3FAA) and L₄ with cancer‐related EphA2 protein kinases (1MQB) with binding energy ?10.61 kcal/mol, ?10.02 kcal/mol and inhibition constant 16.67 nm and 45.41 nm , respectively. The binding energies of L₁ – L₄ are comparable with binding energies of their proven inhibitors. L₁ , L₃ and L₄ can be considered as both 3FAA and 1MQB dual targeting anticancer agents, while L₁ and L₃ are both 2VY7 and 2WCX dual targeting antiviral agents. On the other side, L₂ and L₄ target only one virus related target (2WCX). Furthermore, the geometry optimizations of L₁ – L₄ were performed via density functional theory (DFT). Moreover, all four ligands ( L₁ – L₄ ) were characterized by NMR, FT‐IR, ESI‐MS, elemental analysis and their molecular structures were validated by single crystal X‐ray diffraction studies.     

Synthesis,Biological Activity Evaluation and Molecular Docking of Imidazole Derivatives Possessing Hydrazone Moiety

In an attempt to identify potential active anticancer agents with low cytotoxic properties and CA inhibitors, a new series of hybrid compounds incorporating imidazole ring and hydrazone moiety as part of their structure were synthesized by aza-Michael addition reaction followed by intramolecular cyclization. The structure of synthesized compounds was elucidated using various spectral techniques. Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with K_i values in range of 17.53±7.19–150.50±68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26–153.27±55.80 nM against dominant cytosolic hCA II isoforms associated with glaucoma. Furthermore, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities. The proteins used for the calculations are prostate cancer protein (PDB ID: 3RUK and 6XXP). ADME/T analysis was carried out to examine the drug properties of the studied molecules.     

Synthesis and Characterization of Novel 1,3-Diaryltriazene-Substituted Sulfaguanidine Derivatives as Selective Carbonic Anhydrase Inhibitors: Biological Evaluation,in Silico ADME/T and Molecular Docking Study

Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial, glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives ( SG1-13 ) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with K_I values in the range of 6.44±0.74-86.85±7.01 nM for hCA I and with K_I values in the range of 8.16±0.40-77.29±9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors. These compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.     

Design,Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

In recent years, numerous studies have reported on the anti-tumor properties of artemisinin and its derivatives. However, the relationship between their artemisinin chirality and activity remains unknown. In this study, we synthesized a series of artemisinin dimer derivatives with three different chiral structures and tested their antiproliferative activity in MCF-7 and HepG2 cells using the CCK-8 assay. Interestingly, we discovered that artemisinin dimer derivatives with β, β and α, β conformations at C-10 exhibited stronger anti-tumor activity than those with an α, α configuration in MCF-7 and HepG2 cells. Notably, compound 4 showed an activity of 0.06 μM in MCF-7 cells. This study demonstrates the relationship between the conformation and activity of artemisinin dimer derivatives, and these derivatives have the potential to be developed into anti-cancer drugs.     

Quinoline Based Monocarbonyl Curcumin Analogs as Potential Antifungal and Antioxidant Agents: Synthesis,Bioevaluation and Molecular Docking Study

In search for new fungicidal and free radical scavenging agents, we synthesized a focused library of 2‐chloroquinoline based monocarbonyl analogs of curcumin (MACs). The synthesized MACs were evaluated for in vitro antifungal and antioxidant activity. The antifungal activity was evaluated against five different fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger, and Cryptococcus neoformans, respectively. Most of the synthesized MACs displayed promising antifungal activity compared to the standard drug Miconazole. Furthermore, molecular docking study on a crucial fungal enzyme sterol 14α‐demethylase (CYP51) could provide insight into the plausible mechanism of antifungal activity. MACs were also screened for in vitro radical scavenging activity using butylated hydroxytoluene (BHT) as a standard. Almost all MACs exhibited better antioxidant activity compared to BHT.     

Molecular Design,Synthesis and Docking Study of Alkyl and Benzyl Derivatives of Robustic Acid as Topoisomerase I Inhibitors

Robustic acid is reported to be a bioactive compound, isolated from the medicinal plant Dalbergia benthamii Prain . Ten alkyl and benzyl derivatives ( 2a – 2j ) of robustic acid were designed and synthesized based on molecular docking approaches. The biological activities of most of the synthesized compounds (such as 2g , 2h , and 2i ) were closely consistent with the docking results. In particular, 4‐O‐phenylpropyl substituted compound 2g displayed potent topoisomerase I inhibitory activity as well as cytotoxicity against SMMC‐7721, HepG2, and HeLa cell lines. Further biological testing suggests that compound 2g acted mainly by an arrest of the tumor cells in G1 phase of the cell cycle and suppressed cell proliferation by inducing apoptosis. The findings of this study are encouraging with respect to potential utilization of these compounds as new topoisomerase I inhibitors.     

Design,Synthesis and Molecular Docking of 1,3,4-Oxadiazole-2(3H)-thione Derivatives Containing 1,4-Benzodioxane Skeleton as Potential FabH Inhibitors

Fatty acid biosynthesis is essential for bacterial survival. Of these promising targets, β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target. A series of novel 1,3,4-oxadiazole-2(3H)-thione derivatives containing 1,4-benzodioxane skeleton targeting FabH were designed and synthesized. These compounds were determined by ¹H-NMR, ¹³C-NMR, MS and further confirmed by crystallographic diffraction study for compound 7m and 7n . Most of the compounds exhibited good inhibitory activity against bacteria by computer-assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compounds 7e and 7q exhibited the most significant inhibitory activities. Besides, compound 7q showed the best E. coli FabH inhibitory activity (IC₅₀=2.45 μΜ). Computational docking studies also showed that compound 7q interacts with FabH critical residues in the active site.