Quinoline Derivatives Research Articles

Inhibition of apoptosis and biofilm formation in Candida auris by click-synthesized triazole-bridged quinoline derivatives.

Candida auris, a recent addition to the Candida species, poses a significant threat with its association to numerous hospital outbreaks globally, particularly affecting immunocompromised individuals. Given its resistance to existing antifungal therapies, there is a pressing need for innovative treatments. In this study, novel triazole bridged quinoline derivatives were synthesized and evaluated for their antifungal activity against C. auris. The most promising compound, QT7, demonstrated exceptional efficacy with a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 0.12 μg mL-1 and 0.24 μg mL-1, respectively. Additionally, QT7 effectively disrupted mature biofilms, inhibiting them by 81.98% ± 8.51 and 89.57 ± 5.47 at MFC and 2× MFC values, respectively. Furthermore, QT7 induced cellular apoptosis in a dose-dependent manner, supported by various apoptotic markers such as phosphatidylserine externalization, mitochondrial depolarization, and reduced cytochrome c and oxidase activity. Importantly, QT7 exhibited low hemolytic activity, highlighting its potential for further investigation. Additionally, the physicochemical properties of this compound suggest its potential as a lead drug candidate, warranting further exploration in drug discovery efforts against Candida auris infections.

Visible-light-driven synthesis of indoles via aerobic oxidative dehydrogenation at room temperature

A photo-induced synthesis strategy has been developed to produce indole and other N-heterocycles via aerobic oxidative dehydrogenation. This process was performed under air at room temperature, resulting in moderate to good yields of indole, furan, quinoline and isoquinoline derivatives. Various sensitive functional groups are well tolerated in this reaction. This method is economical, highly efficient, and environmentally friendly, providing inspiration for the development of novel photochemical synthesis reactions.

Synthesis, insecticidal Activity, and molecular docking analysis of some benzo[h]quinoline derivatives against Culex pipiens L. Larvae

Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.

A New Method of Constructing Methyleneindene and Quinoline Frameworks from Methylenecyclopropanes.

In this paper, we have established an operationally convenient protocol for the rapid construction of polysubstituted methyleneindene and quinoline derivatives under mild conditions. This new synthetic method is achieved through the conversion of acetyl-substituted methylenecyclopropanes with TsOH ⋅ H2O and ortho-amino-substituted methylenecyclopropanes with aromatic aldehyde and TsOH ⋅ H2O, respectively. A variety of transformations of the obtained products was demonstrated. The plausible reaction mechanisms were also proposed.

SYNTHESIS AND STRUCTURE OF SOME 8-METHOXY-2-ARYLQUINOLIN-7-OL DERIVATIVES FROM VANILLIN

The key compound, 4-hydroxy-3-methoxy-2-nitrobenzaldehyde (3), was synthesized from vanillin by esterification, nitration, and hydrolysis. The aldol condensation reaction of compound 3 was performed with aryl methyl ketones to obtain two chalcones 4a and 4b. The reduction reactions of these chalcones 4a and 4b were performed using SnCl2 in HCl to obtain two 8-methoxy-2-arylquinolin-7-ol derivatives 5a and 5b. The structures of the two quinoline derivatives were confirmed by 1H-NMR, 13C-NMR spectroscopic methods and MS and HRMS spectrometry.

Novel Quinoline‐Based RAF Inhibitors: A Comprehensive Review on Synthesis, SAR and Molecular Docking Studies

AbstractThe RAF (rapidly accelerated fibrosarcoma) kinases play critical roles in a variety of different cellular processes, including the advancement of the cell cycle, the proliferation of cells, the metabolism of cells, cell migration, and the differentiation of cells. RAF kinase was thus established as an important target for the management of cancer disease. RAF inhibitors have elicited remarkable responses and enhanced survival rates in patients with BRAF‐V600E/K melanoma, but their efficacy is restricted by resistance as a result of mutations in RAF, presenting challenges in the identification of novel RAF inhibitors. This has resulted in the development of two generations of RAF inhibitors. In the past years, a variety of heterocyclic scaffolds that are capable of inhibiting RAF activity have been discovered. Quinoline, a molecule with a fused benzene ring and N‐heterocyclic pyridine, is a prime template for designing a variety of new anticancer drugs. In the last few years, quinoline derivative has been studied for their capability to inhibit RAF kinases. In this review, we have summarized synthesis, biological study, and molecular docking studies of substituted quinoline derivatives, which have shown potent anticancer activity by inhibiting the RAF kinases. The present review would help medicinal chemists streamline and guide their efforts toward developing novel quinoline‐based RAF inhibitors, which will be beneficial for drug development.

Revolutionizing Indole Synthesis: A Microwave‐Powered Approach

AbstractTempted by the unique medicinal and biological potential of indole‐containing heterocycles, chemists, especially those specializing in heterocycle synthesis and drug discovery, are actively pursuing their efficient construction. This review spotlights the latest advancements in microwave‐assisted (M. W.) synthesis of diverse indole‐based heterocyclic compounds. We systematically categorize the reported methods based on the specific indole substitution patterns. This review concise the microwave assisted synthesis of indole based‐pyridine derivatives, indole based‐pyrimidine, indole based‐oxindole, spiro‐oxindole, Fischer indole Heck‐isomerization derivatives, functionalized indole, substituted indoles, indolyl quinoline, indole triazole and indolylnicotinonitriles derivatives. Ultimately, this review aims to provide organic and medicinal chemists with a concise yet informative guide to recent methodologies employing indole derivatives in the microwave‐powered synthesis of heterocycles.

Novel quinoline substituted autophagy inhibitors attenuate Zika virus replication in ocular cells

Zika virus (ZIKV) is a re-emerging RNA virus that is known to cause ocular and neurological abnormalities in infants. ZIKV exploits autophagic processes in infected cells to enhance its replication and spread. Thus, autophagy inhibitors have emerged as a potent therapeutic target to combat RNA viruses, with Hydroxychloroquine (HCQ) being one of the most promising candidates. In this study, we synthesized several novel small-molecule quinoline derivatives, assessed their antiviral activity, and determined the underlying molecular mechanisms. Among the nine synthesized analogs, two lead candidates, labeled GL-287 and GL-382, significantly attenuated ZIKV replication in human ocular cells, primarily by inhibiting autophagy. These two compounds surpassed the antiviral efficacy of HCQ and other existing autophagy inhibitors, such as ROC-325, DC661, and GNS561. Moreover, unlike HCQ, these novel analogs did not exhibit cytotoxicity in the ocular cells. Treatment with compounds GL-287 and GL-382 in ZIKV-infected cells increased the abundance of LC3 puncta, indicating the disruption of the autophagic process. Furthermore, compounds GL-287 and GL-382 effectively inhibited the ZIKV-induced innate inflammatory response in ocular cells. Collectively, our study demonstrates the safe and potent antiviral activity of novel autophagy inhibitors against ZIKV.

Novel neuroprotective 5,6-dihydropyrido[2′,1':2,3]imidazo[4,5-c]quinoline derivatives acting through cholinesterase inhibition and CB2 signaling modulation

A novel group of 5,6-dihydropyrido [2′,1':2,3]imidazo [4,5-c]quinolines was prepared via a microwave assisted one-pot telescopic approach. The synthetic sequence involves the formation of an amine precursor of imidazo [1,2-a]pyridine via condensation and reduction under microwave irradiation. Subsequently, the Pictet-Spengler cyclisation reaction occurs with ketones (cyclic or acyclic) to obtain substituted 5,6-dihydropyrido [2′,1':2,3]imidazo [4,5-c]quinolines in excellent yields. The compounds were tested as neuroprotective agents. Observed protection of neuron-like cells, SH-SY5Y differentiated with ATRA, in Parkinson's and Huntington's disease models inspired further mechanistic studies of protective activity against damage induced by 1-methyl-4-phenylpyridinium (MPP+), a compound causing Parkinson's disease. The novel compounds exhibit similar or higher potency than ebselen, an established drug with antioxidant activity, in the cells against MPP + -induced total cellular superoxide production and cell death. However, they exhibit a significantly higher capacity to reduce mitochondrial superoxide and preserve mitochondrial membrane potential. We also observed marked differences between a selected derivative and ebselen in terms of normalizing MPP + -induced phosphorylation of Akt and ERK1/2. The cytoprotective activity was abrogated when signaling through cannabinoid receptor CB2 was blocked. The compounds also inhibit both acetylcholine and butyrylcholine esterases. Overall the data show that novel 5,6-dihydropyrido [2′,1':2,3]imidazo [4,5-c]quinoline have a broad cytoprotective activity which is mediated by several mechanisms including mitoprotection.

Circularly Polarized Room Temperature Phosphorescence through Twisting‐Induced Helical Structures from Polyvinyl Alcohol‐Based Fibers Containing Hydrogen‐Bonded Dyes

AbstractRoom temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting‐induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q‐NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP‐RTP) is readily achieved by imparting left‐ or right‐hand helical structure through simply twisting, enabling large‐scale production of chiral Q‐NH2@PVA fiber with dissymmetry factor of 10−2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA‐based fibers with outstanding adaptivity in cutting‐edge anti‐counterfeiting technology.

Circularly Polarized Room Temperature Phosphorescence through Twisting-Induced Helical Structures from Polyvinyl Alcohol-Based Fibers Containing Hydrogen-Bonded Dyes.

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6 %, and the improved tensile strength being 1.7 times than pure PVA fiber (172±5.82 vs 100±5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity.

TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC50 = 0.85 μM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity and adjuvant potential alone or in combination with alum. Most of the phenolic derivatives were more active than BBIQ and, except for 12b, all were TLR7 specific. Although the synthesized compounds were less active than resiquimod, the immunization data on combination with alum, specifically the IgG1, IgG2b and IgG2c responses, were superior in comparison to BBIQ as well as the reference standard resiquimod. Compound 12b was 5-fold more potent (EC50 = 0.15 μM in TLR7) than BBIQ and induced double the IgG response to SARS-CoV-2 and hepatitis antigens. Similarly, compound 12c (EC50 = 0.31 μM in TLR7) was about 3-fold more potent than BBIQ and doubled the IgG levels. Even though compound 12d exhibited low TLR7 activity (EC50 = 5.13 μM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response.

Cu‐Catalyzed Synthesis of Coumarin‐1,2,3‐Triazole Hybrids connected with Quinoline or Pyridine Framework**

AbstractCoumarin‐1,2,3‐triazole hybrids connected to quinoline or pyridine framework have been synthesized in good to excellent yield by the 1,3‐dipolar azide alkyne cycloaddition reaction (CuACC) of 4‐azidocoumarin with propargyl quinoline or propargyl pyridine derivatives in the presence of CuSO4.5H2O or CuI as catalyst. Similar reaction of 4‐azidocoumarin or tetrazolo[1,5‐a]pyridine with 4‐propargyloxycoumarin and 4‐propargylaminocoumarin resulted in the synthesis of the corresponding coumarin‐1,2,3‐triazole hybrids. Some preliminary screening test for some biological activities of new compounds have been performed.

Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model

BackgroundIt is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics.ResultsThe bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively.In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1β), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL.Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues.ConclusionCombining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Ratiometric two-photon fluorescent probe for imaging hydrogen peroxide during stroke-induced ferroptosis

Ischemic stroke (IS) initiates a programmed cell death through apoptosis, autophagy, and ferroptosis, which results in neuronal damage and brain injury. However, existing methods for in situ detection of ferroptosis are currently insufficient. Therefore, we constructed a series of hydrogen peroxide (H2O2—one of the major ROS) probes (QH2O2, MQH2O2, and BQH2O2) with quinoline derivatives as two-photon fluorophores and boronate as the recognition domain. Experimental results indicated that the linear response range of the probe MQH2O2 to H2O2 increased from < 10–300 μM as compared with the probe QH2O2. Moreover, the linear correlation coefficient also increased from 0.9012 to 0.999, indicating that the ratiometric fluorescent probe has built-in corrections for environmental interference, which allows a more accurate fluorescence analysis. Modification of the probe by connecting triethylene glycol monomethyl ether (BQH2O2) increased the lipophilic index of the probe to 2.01, which enhanced its ability to cross the blood–brain barrier. Therefore, the developed probe is useful for analyzing the H2O2 production during an ischemic stroke and its fluctuation with ferroptosis.

Electronic structure modulation in quinoline derivatives through substituent-mediated effects: Development of AIE fluorescent probes for Fe3+ detection in water samples

Iron (Fe3+) is an essential trace element in biological organisms. Abnormal concentrations of Fe3+ in aquatic possess the potential to disrupt normal physiological and metabolic processes in living organisms. Consequently, the pursuit of developing fluorescent probes for detecting Fe3+ concentrations in water samples is highly significant. The lone electron pair on the nitrogen atom of quinoline demonstrates outstanding coordination capabilities, enabling the selective detection of metal ions through coordination. Nevertheless, the interaction between metal ions and quinoline-based fluorescent probes tends to lead to nanoparticle aggregation, causing aggregation-caused quenching (ACQ) phenomena. This severely restricts the practical application of these probes. To address this challenge, the study utilizes quinoline as the foundational framework and modulates the excited-state electronic structure of quinoline derivatives through substituent effects. This facilitates the transition from ACQ to aggregation-induced emission (AIE). By integrating theoretical calculations, the paper proposes a comprehensive strategy for designing AIE molecules based on quinoline. This contribution provides innovative perspectives on AIE molecule design. Ultimately, the AIE property of the 8-MQB molecule is harnessed to develop a fluorescent probe capable of detecting Fe3+ in water samples. The fluorescence intensity exhibits a robust linear correlation with Fe3+ concentrations within the range of 5.0 μM to 0.3 mM. Moreover, the probe demonstrates exceptional resistance to interference from other metal ions. In conclusion, this research presents a universal strategy for designing AIE molecules and introduces an AIE probe for the rapid detection of Fe3+ concentrations in water samples.

Degradation of hydroxychloroquine in aqueous solutions under electron beam treatment

Abstract Hydroxychloroquine (HCQ), a 4-amino quinoline derivative, has antimalarial and anti-inflammatory activity and was most recently proposed in the treatment of SARS-COVID-19. Its pharmacokinetics and toxic side effects necessitate the monitoring of its presence in the environment and its removal from wastewater. In this study, HCQ was removed from an aqueous solution with a removal efficiency of between 80% and 90% under electron beam (EB) irradiation. The degradation of HCQ was propagated by reactions involving both the hydroxyl radical and aqueous electron. The degradation was observed to follow a pseudo-first-order kinetic reaction. The applied radiation dose, pH, and initial HCQ concentration were influential in the degradation efficiency under EB irradiation. Acidic and alkaline pH favored the removal of HCQ under EB irradiation. Even though the initial HCQ was successfully degraded, it was not completely mineralized. The TOC and chemical oxygen demand (COD) remained at a relatively stable level following EB irradiation of the aqueous solutions. This is attributed to the formation of other organic compounds that were not degraded under the investigated experimental conditions.

RECENT INNOVATIONS IN ORGANIC INHIBITORS FOR MILD STEEL IN CORROSIVE SOLUTIONS: A MINI REVIEW

Corrosion of mild steel in corrosive solutions is one of the major concerns in industries such as oil and gas, petrochemical and marine. The use of organic inhibitors has proven to be an effective method to protect mild steel from corrosion. This mini-review summarised recent innovations in organic inhibitors for mild steel in corrosive solutions. This article discusses the types of organic inhibitors, including adsorption, film-forming, mixed, synergistic and green inhibitors, their mechanism of action, and their application in various corrosive environments. The article then highlights recently published inhibitors such as quinoline derivatives, Schiff bases, amino acids, and polymers. These inhibitors have shown promising results in protecting mild steel from corrosion. The mini-review concludes by discussing the prospects of organic inhibitors for mild steel in corrosive solutions. Overall, this mini-review provides valuable insights into recent innovations in organic inhibitors for mild steel in corrosive solutions, which are useful for researchers and industries working on corrosion protection.

Cytotoxic Cu(II) Complexes with a Novel Quinoline Derivative Ligand: Synthesis, Molecular Docking, and Biological Activity Analysis.

The utilization of metallodrugs as a viable alternative to organic molecules has gained significant attention in modern medicine. We hereby report synthesis of new imine quinoline ligand (IQL)-based Cu(II) complexes and evaluation of their potential biological applications. Syntheses of the ligand and complexes were achieved by condensation of 7-chloro-2-hydroxyquinoline-3-carbaldehyde and 2,2'-thiodianiline, followed by complexation with Cu(II) metal ions. The synthesized ligand and complexes were characterized using UV-vis spectroscopy, TGA/DTA, FTIR spectroscopy, 1H and 13C NMR spectroscopy, and pXRD. The pXRD diffractogram analysis revealed that the synthesized ligand and its complexes were polycrystalline systems, with nanolevel average crystallite sizes of 13.28, 31.47, and 11.57 nm for IQL, CuL, and CuL 2 , respectively. The molar conductivity confirmed the nonelectrolyte nature of the Cu(II) complexes. The biological activity of the synthesized ligand and its Cu(II) complexes was evaluated with in vitro assays, to examine anticancer activity against the MCF-7 human breast cancer cell line and antibacterial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. The CuL complex had the highest cytotoxic potency against MCF-7 breast cancer cells, with an IC50 of 43.82 ± 2.351 μg/mL. At 100 μg/mL, CuL induced the largest reduction of cancer cell proliferation by 97%, whereas IQL reduced cell proliferation by 53% and CuL 2 by 28%. The minimum inhibitory concentration for CuL was found to be 12.5 μg/mL against the three tested pathogens. Evaluation of antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl revealed that CuL exhibited the highest antioxidant activity with IC50 of 153.3 ± 1.02 μg/mL. Molecular docking results showed strong binding affinities of CuL to active sites of S. aureus, E. coli, and estrogen receptor alpha, indicating its high biological activity compared to IQL and CuL 2 .

Theoretical Investigation and Design of Bioactive Quinoline Derivatives as Inhibitors of DNA Gyrase of Salmonella typhi

The ever-increasing rate of resistance to existing antibiotics by Salmonella typhi has made the search for novel drug candidates a necessity. In this study, Molecular docking technique was used to screen 18 bioactive quinoline derivatives against DNA gyrase of Salmonella typhi using PyRx graphical user interface of AutoDock Vina software. Ligand with the best binding affinity against the target macromolecule was used as prototype to design novel analogues with enhanced potencies. With the aid of Swiss ADME online server and Osiris DataWarrior v5.5.0 programme, the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of the ligands were evaluated and their electronic properties were computed using density functional theory (DFT) method of Spartan 14.0 software. Ligand 3 (L3) with the best binding affinity (TG) value of −10.5 kcal/mol was chosen as a prototype to design La and Lb with TG value of −10.7 kcal/mol and −10.8 kcal/mol; binding constant (ka) of 7.04 × 107 and 8.35 × 107 ; and dissociation constant (kd) of 1.42 x 10−8 and 1.2 × 10−8, respectively. When compared with ciprofloxacin (TG = −7.7 kcal/mol), the ligands could be more potent. Likewise, the ligands were found to possess excellent oral bioavailability and pharmacokinetic profiles. Furthermore, DFT calculations on La and Lb revealed that they possess highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap of 3.46 eV and 3.45 eV; and global electrophilicity index of 3.83 eV and 3.96 eV, respectively. The designed ligands tend to be consistent with all the validation protocols deployed in this study and as such could be recommended as novel drug candidates for treatment of Salmonella typhi induced salmonellosis.