Compounds 3f Research Articles

Design, synthesis and anti-inflammatory assessment of certain substituted 1,2,4-triazoles bearing tetrahydroisoquinoline scaffold as COX 1/2-inhibitors

Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was synthesized and evaluated as inhibitors of COX-1 and COX-2. In order to overcome the adverse effects of highly selective COX-2 and non-selective COX-2 inhibitors, the compounds of this study were designed with the goal of obtaining moderately selective COX-2 inhibitors. In this study compounds 9e, 9g and 11f are the most effective derivatives against COX-2 with IC50 values 0.87, 1.27 and 0.58 µM, respectively which are better than or comparable to the standard drug celecoxib (IC50 = 0.82 µM) but with lower selectivity indices as required by our goal design. The results of the in vivo anti-inflammatory inhibition test revealed that compounds 9e, 9g and 11f displayed a higher significant anti-inflammatory activity than celecoxib at all-time intervals. In addition, these compounds significantly decreased the production of inflammatory mediators PGE-2, TNF-ɑ and IL-6. Compounds 9e, 9g and 11f had a safe gastric profile compared to indomethacin, also compound 11f (ulcerogenic index = 1.33) was less ulcerous than the safe celecoxib (ulcerogenic index = 3). Moreover, histopathological investigations revealed a normal architecture of both paw skin and gastric mucosa after oral treatment of rats with compound 11f. Furthermore, molecular docking studies were performed on COX-1 and COX-2 to study the binding pattern of compounds 9e, 9g and 11f on both isoenzymes.

Effect of Three Novel Thiazolidiones on the Development, Reproduction, and Trehalase Activity of Spodoptera frugiperda (Lepidoptera: Noctuidae)

Spodoptera frugiperda was used to investigate its role as a trehalase inhibitor of three new thiothiazolidone compounds—6d, 6e, and 6f. The development and reproduction of S. frugiperda were investigated to evaluate the potential of these compounds as a novel pesticide for pest control. Compounds 6d, 6e, and 6f were injected into larvae and female pupae. Molecular changes in trehalose and chitin metabolism genes were monitored. Pupal trehalase activity, the female pupal emergence rate, ovarian development, and SfVg and SfVgR gene expression levels were assessed. The results revealed that all three compounds significantly inhibited trehalase activity in the larvae. The expression of TRE was significantly downregulated, and compounds 6d and 6f significantly downregulated the expression of TRE2. Treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormalities. The egg production and hatching rates were markedly diminished by the inhibitors, and the ovaries displayed blackening and clumping. These compounds exhibit promise as eco-friendly insecticides, but further experiments are required to test their multifaceted capabilities.

Synthesis and antiproliferative activity of CBD aromatic ester derivatives

This study involved the synthesis of a series of novel cannabidiol (CBD) aromatic ester derivatives, including CBD-8,12-diaromaticester derivatives (compounds 2a–2t) and CBD-8,12-diacetyl-21-aromaticester derivatives (compound 5a–5c). The antiproliferative activities of these compounds against human liver cancer cell lines HePG2 and HeP3B as well as human pancreatic cancer cell lines ASPC-1 and BXPC-3 were evaluated in vitro using the CCK-8 assay. The results indicated that compound 2f exhibited an IC50 value of 2.75 µM against HePG2, which is 5.32-fold higher than that of CBD. Additionally, compounds 2b and 5b demonstrated varying degrees of improved anticancer activity (IC50 5.95-9.21 µM) against HePG2.

Synthesis of Bisindole Alkaloids and Their Mode of Action against Methicillin-Resistant Staphylococcus Aureus.

About 100,000 deaths are attributed annually to infections with methicillin-resistant Staphylococcus aureus (MRSA) despite concerted efforts toward vaccine development and clinical trials involving several preclinically efficacious drug candidates. This necessitates the development of alternative therapeutic options against this drug-resistant bacterial pathogen. Using the Masuda borylation-Suzuki coupling (MBSC) sequence, we previously synthesized and modified naturally occurring bisindole alkaloids, alocasin A, hyrtinadine A and scalaradine A, resulting in derivatives showing potent in vitro and in vivo antibacterial efficacy. Here, we report on a modified one-pot MBSC protocol for the synthesis of previously reported and several undescribed N-tosyl-protected bisindoles with anti-MRSA activities and moderate cytotoxicity against human monocytic and kidney cell lines. In continuation of the mode of action investigation of the previously synthesized membrane-permeabilizing hit compounds, mechanistic studies reveal that bisindoles impact the cytoplasmic membrane of Gram-positive bacteria by promiscuously interacting with lipid II and membrane phospholipids while rapidly dissipating membrane potential. The bactericidal and lipid II-interacting lead compounds 5c and 5f might be interesting starting points for drug development in the fight against MRSA.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 μg/mL, and some title compounds were active towards Nilaparvata lugens at 500 μg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 μg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 μg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Novel indazolylchromones: synthesis, fungicidal evaluation, molecular docking and aquatic toxicity prediction.

Fungal diseases cause substantial loss to agricultural crops, affecting both quantities and quality. Although several methods are used for preventing disease incidence, fungicides remain crucial for higher yields and better quality. But in the past, the efficacy of several fungicides has decreased due to increased cases of fungicide resistant. In our pursuit of new effective fungicides, we synthesised a series of twenty 2-Indazol-1-yl-chromen-4-one derivatives (6a- 6t). The characterization of synthesized compounds was performed by several spectroscopic methods including Infrared, Nuclear Magnetic Resonance (1H and 13C) and HRMS. Out of 20 synthesised compounds, 19 (6b- 6t) were found to be novel. All synthesised indazolylchromones showed very good antifungal activity against Sclerotium rolfsii and Fusarium oxysporum. Among the tested compounds, 6t and 6f exhibited very good fungicidal activity against S. rolfsii with an ED50 of 10.10mgL-1 and 16.18mgL-1, respectively. In case of Fusarium oxysporum compound 6f displayed good' activity with an ED50 value of 27.82mgL-1. Molecular docking study was done to predict the binding sites of most active compounds, 6t and 6f with Cytochrome P450 14alpha -sterol demethylase (CYP51) enzyme using molsoft software. The acute toxicity predictions the of synthesized compounds for fish (LC50,96 Hr), daphnid (LC50, 48 Hr) and green algae (EC50, 96Hr) and the chronic toxicity predictions (ChV) were assessed using Ecological Structure Activity Relationship (ECOSAR) model. As per ECOSAR prediction, all the chemicals are inside AD and not missing predictions.

Design, synthesis, and anti-oomycete activity of 3-acyloxymaltol/ethyl maltol derivatives

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.

Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties.

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060μg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050μg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin's IC50 value of 11µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.

Lead Identification of Novel Naphthyridine Derivatives as Potent SOS1 Inhibitors.

SOS1, a guanine nucleotide exchange factor (GEF), plays a critical role in catalyzing the conversion of KRAS from its GDP- to GTP-bound form, regardless of KRAS mutation status, and represents a promising new drug target to treat all KRAS-driven tumors. Herein, we employed a scaffold hopping strategy to design, synthesize, and optimize a series of novel binary ring derivatives as SOS1 inhibitors. Among them, compound 10f (HH0043) displayed potent activities in both biochemical and cellular assays and favorable pharmacokinetic profiles. Oral administration of HH0043 resulted in a significant tumor inhibitory effect in a subcutaneous KRAS G12C-mutated NCI-H358 (human lung cancer cell line) xenograft mouse model, and the tumor inhibitory effect of HH0043 was superior to that of BI-3406 at the same dose (total growth inhibition, TGI: 76% vs 49%). On the basis of these results, HH0043, with a novel 1,7-naphthyridine scaffold that is distinct from currently reported SOS1 inhibitors, is nominated as the lead compound for this discovery project.

Pyrazole-thiazole hybrids: Synthesis, computational studies and impact on digestive enzymes

In this study, the syntheses of some pyrazole-thiazole hybrids and their cyanoacrylate derivatives have been reported. 1H NMR, 13C NMR, LC-MS, and IR spectroscopy were used to characterize all the synthesized compounds. DFT studies have been employed to assess the electronic properties of the synthesized compounds. To ensure the necessary metabolization of the synthesized compounds, their safety profiles were assessed using the Vnn-ADMAT tool. Docking studies investigated the interactions between the synthesized compounds (6a-h and 8a-h) and the active sites of gastric enzymes α-Amylase, Trypsin, and Pepsin with binding affinities (kcal mol−1) ranging from 6.0 to 8.1, 6.7 to 8.5, and 7.7 to 8.6, respectively. Both pyrazole-thiazole hybrids and their cyanoacrylate derivatives demonstrated efficient anti-gastric activities. Varying levels of inhibition were observed among the analogs, such as compound 8f exhibiting the highest inhibitory activity at 61.93 % against α-Amylase at 10−7M, compound 6e showed best inhibition at 68.09 % against Trypsin at 10−7M, and compound 6c displayed remarkable inhibition at 69.51 % against Pepsin at 10−7M. The synthesized compounds exhibited selectivity for α-Amylase.

Synthesis of Novel Fluoro Phenyl Triazoles Via Click Chemistry with or without Microwave Irradiation and their Evaluation as Anti-proliferative Agents in SiHa Cells.

Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Synthesis of new N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives and evaluation of their AChE, BChE, and BACE-1 inhibitory activities.

In this study, the synthesis of N-(5,6-methylenedioxybenzothiazole-2-yl)-2-[(substituted)thio/piperazine]acetamide/propanamide derivatives (3a-3k) and to investigate their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase 1 (BACE-1) inhibition activity were aimed. Mass, 1H NMR, and 13C NMR spectra were utilized to determine the structure of the synthesized compounds. Compounds 3b, 3c, 3f, and 3j showed AChE inhibitory activity which compound 3c (IC50 = 0.030 ± 0.001 µM) showed AChE inhibitory activity as high as the reference drug donepezil (IC50 = 0.0201 ± 0.0010 µM). Conversely, none of the compounds showed BChE activity. Compounds 3c and 3j showed the highest BACE-1 inhibitory activity and IC50 value was found as 0.119 ± 0.004 µM for compound 3j whereas IC50 value was 0.110 ± 0.005 µM for donepezil, which is one of the reference substance. Molecular docking studies have been carried out using the data retrieved from the server of the Protein Data Bank (PDBID: 4EY7 and 2ZJM). Using in silico approach behavior active compounds (3c and 3j) and their binding modes clarified.

Next generation imidazothiazole and imidazooxazole derivatives as potential drugs against brain-eating amoebae.

Managing primary amoebic meningoencephalitis, induced by Naegleria fowleri poses a complex medical challenge. There is currently no specific anti-amoebic drug that has proven effectiveness against N. fowleri infection. Ongoing research endeavours are dedicated to uncovering innovative treatment strategies, including the utilization of drugs and immune modulators targeting Naegleria infection. In this study, we explored the potential of imidazo[2,1-b]thiazole and imidazooxazole derivatives that incorporate sulfonate and sulfamate groups as agents with anti-amoebic properties against N. fowleri. We assessed several synthesized compounds (1f, 1m, 1q, 1s,and 1t) for their efficacy in eliminating amoebae, their impact on cytotoxicity, and their influence on the damage caused to human cerebral microvascular endothelial (HBEC-5i) cells when exposed to the N. fowleri (ATCC 30174) strain. The outcomes revealed that, among the five compounds under examination, 1m, 1q, and 1t demonstrated notable anti-parasitic effects against N. fowleri (P ≤ 0.05). Compound 1t exhibited the highest anti-parasitic activity, reducing N. fowleri population by 80%. Additionally, three compounds, 1m, 1q, and 1t, significantly mitigated the damage inflicted on host cells by N. fowleri. However, the results of cytotoxicity analysis indicated that while 1m and 1q had minimal cytotoxic effects on endothelial cells, compound 1t caused moderate cytotoxicity (34%). Consequently, we conclude that imidazo[2,1-b]thiazole and imidazooxazole derivatives containing sulfonate and sulfamate groups exhibit a marked capacity to eliminate amoebae viability while causing limited toxicity to human cells. In aggregate, these findings hold promise that could potentially evolve into novel therapeutic options for treating N. fowleri infection.

Thiazolidinone-linked-1,2,3-triazoles with (R)-Carvone as new potential anticancer agents.

Aim: This study explores the cytotoxic and apoptotic effects of novel thiazolidinone-1,2,3-triazole hybrids on HT-1080, A-549, and MDA-MB-231 cancer cell lines.Methods & results: The synthesized compounds underwent comprehensive characterization (NMR and HRMS) to confirm their structures and purity. Subsequent anticancer activity screening across diverse cancer cell lines revealed promising antitumor potential notably, compounds 6f and 6g. Mechanistic investigations unveiled that compound 6f triggers apoptosis through the caspase-3/7 pathway. In terms of in silico studies, the compound 6f was identified as a potent inhibitor of caspase-3 and caspase-7.Conclusion: The present study underscores the therapeutic potential of thiazolidinone-1,2,3-triazole hybrids against certain cancer cells. These findings highlight a promising avenue for the development of cancer treatment strategies utilizing these (R)-Carvone-based derivatives.

Synthesis, Characterization, DFT mechanistic study, Antibacterial Activity, Molecular modeling, and ADMET properties of novel chromone-isoxazole hybrids

A series of novel hybrid heterocycles incorporating isoxazole rings have been successfully synthesized, characterized, and evaluated for their antibacterial responses. The synthesized compounds were obtained by a subsequent N-alkylation and 1,3-dipolar cycloaddition reactions, their structures were identified by spectroscopy techniques (1H NMR, 13C NMR and 2D HSQC), and confirmed by mass spectrometry (HRMS). The spectroscopic data also show that the 1,3-dipolar cycloaddition (1,3-DC) reactions proceed in a regiospecific manner to give only one cycloadduct. The observed regioselectivity and the mechanistic study of the 1,3-DC reaction were further highlighted and explained using Density Functional Theory (DFT) calculations with the B3LYP/6–31G(d,p) basis set and Electron Localization Function (ELF) analysis. Moreover, the antibacterial screening shows that some compounds exhibit good efficacy against the tested bacterial strains. In addition, molecular docking studies were carried out to highlight the modes of interaction between the most active molecule 5d and receptors of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. The results show that the studied compound was effectively docked to the active sites of each responsible protein with high protein-binding energies in kcal/mol. Finally, the prediction of ADMET properties suggests that almost all the hybrid compounds have good pharmacokinetic profiles, with no observed signs of toxicity, except for compounds 5e, 5f and 5g.

Discovery of Novel Non-Nucleoside Inhibitors Interacting with Dizinc Ions of CD73.

High extracellular concentrations of adenosine triphosphate (ATP) in the tumor microenvironment generate adenosine by sequential dephosphorylation of CD39 and CD73, resulting in potent immunosuppression to inhibit T cell and natural killer (NK) cell function. CD73, as the determining enzyme for adenosine production, has been shown to correlate with poor clinical tumor prognosis. Conventional inhibitors as analogues of adenosine 5'-monophosphate (AMP) may have a risk of further metabolism to adenosine analogues. Here, we report a new series of malonic acid non-nucleoside inhibitors coordinating with zinc ions of CD73. Compound 12f was found to be a superior CD73 inhibitor (IC50 = 60 nM) by structural optimization, and its pharmacokinetic properties were investigated. In mouse tumor models, compound 12f showed excellent efficacy and reversal of immunosuppression in combination with chemotherapeutic agents or checkpoint inhibitors, suggesting that it deserves further development as a novel CD73 inhibitor.

Insight on Some Newly Synthesized Trisubstituted Imidazolinones as VEGFR-2 Inhibitors.

Two series of ten new 1,2,4-trisubstituted imidazolin-5-ones were synthesized and screened against MCF-7 breast cancer and A549 lung cancer cell lines to test their potential in vitro anticancer activity. The results revealed preferential activity of the tested compounds toward MCF-7 cell lines compared to A549 cell lines. The most promising ten compounds (3a, 3c, 3f, 3g, 3h, 3i, 3j, 6a, 6f, and 6i) were subjected to VEGFR-2 enzyme inhibitory activity testing to further explore their mechanism of action. The tested compounds showed remarkable enzyme inhibition in micromolar concentrations ranging from 0.07 to 0.36 μM, compared with Sorafenib and Sunitinib with IC50 values of 0.06 and 0.12 μM, respectively. The most promising candidate, 3j, was further evaluated for its cell cycle phases, apoptotic induction ability, as well as its antiproliferative activity and inhibitory potential for endothelial cell migration, analyzed by a cell scratch assay. Furthermore, in silico studies were also performed to identify and detect the stability of the binding poses.

Newly synthesized based Schiff of phenylferrocene: Molecular and crystal structures, Density Functional Theory calculations, Hirshfeld surface analyses, and improved molecular docking data

In three steps, ferrocene-derived Schiff bases were synthesized, beginning with an arylation reaction, followed by a reduction reaction. The last step describes a condensation reaction between 4-ferrocenylaniline 2a and various aromatic aldehydes in ethanol under reflux. Several techniques were used to determine the structures of the prepared compounds, including 1HNMR , 13CNMR , FTIR, UV/Vis and single crystal X-ray diffraction for compounds 3a, 3f, and 3j. Hirshfeld surface analysis measurements were also performed to measure the interaction energies between molecules. Moreover, the geometric structure of the selected compound (3a, 3f, and 3j) was optimized using a computational analysis involving density functional theory (DFT) calculations based on B3LYP/6–31 G (d, p). Strong binding affinities were observed via both hydrophobic and H-bond interactions with pertinent molecules when molecular docking investigations were conducted on the target crystal structure, the FabX (7e1q). The maximum binding energy is found in the 3d, at -7.99 kcal/mol. Therefore, it is feasible that this structure will work well as a potential lead structure for the synthesis and design of stronger inhibitors that can be used in conjunction with anti-corrosive drugs to treat gastric cancer.

Synthesis and in vitro cytotoxicity of benzoxazole-based PPARα/γ antagonists in colorectal cancer cell lines.

A series of benzoxazole-based amides and sulfonamides were synthesized and evaluated for their human peroxisome proliferator-activated receptor (PPAR)α and PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based on transactivation results, seven compounds were selected to test their in vitro antiproliferative activity in a panel of eight cancer cell lines with different expression rates of PPARα and PPARγ. 3f was identified as the most cytotoxic compound, with higher potency in the colorectal cancer cell lines HT-29 and HCT116. Compound 3f induced a concentration-dependent activation of caspases and cell-cycle arrest in both colorectal cancer models. Docking experiments were also performed to shed light on the putative binding mode of this novel class of dual PPARα/γ antagonists.

Design, synthesis, and structure–activity relationship of 2-chloro-3-formylquinoline containing hybrids as powerful antibacterial agents

This work aims to evaluate the antimicrobial activity of some new quinoline derivatives linked to pyrazole derivatives. The target compounds pyrazolylvinylquinoline 11a-g and 12a-g were achieved by the reaction of 2-chloro-6-nitro-3-quinolinecarboxaldehyde (4) with bromotriphenylphosphonylmethylpyrazole derivatives 9a,b to give the new quinoline derivatives 10a,b which in turn reacted with different aryl amines to afford 11a-g and 12a-g. Pyrazole derivatives 9a,b were obtained by the reaction of hydroxymethylpyrazole derivatives 8a,b with triphenylphosphine hydrobromide. Antimicrobial evaluation of the newly synthesized compounds showed that most of the new compounds appeared active toward Gram-positive bacteria more than Gram-negative bacteria. The biological evaluation of compounds 12d-g displayed the highest antimicrobial activity against the tested microorganism strains. Additionally, compounds 12d and 12f showed excellent activity against P. aeruginosa (MIC50 0.019 mg/mL), while compounds 11d, 11f, 12e, and 12g displayed good activity against the same microorganism (MIC50 0.07 mg/mL). On the other hand, most of the new compounds have moderate activity against E. coli. Compounds 12d and 12f showed excellent activity versus C. albicans in vitro antifungal activity (MIC50 0.15 mg/mL) comparing to or slightly lower than that of Fluconazole. Using molecular docking simulations, we evaluated the binding affinities and interactions of four chosen derivatives 12d-g with a target PDB code 3WT0 protein.