Synthesis and Antibacterial Activity of a New Series of 3‐[3‐(Substituted Phenyl)‐1‐Isonicotinoyl‐1H‐Pyrazol‐5‐yl]‐2H‐Chromen‐2‐one Derivatives

A novel series of 3‐[3‐(substituted phenyl)‐1‐isonicotinoyl‐1H‐pyrazol‐5‐yl]‐2H‐chromen‐2‐one derivatives 4a – k have been synthesized by the reaction of 3‐[2,3‐dibromo‐3‐(substituted phenyl) propanoyl]‐2H‐chromen‐2‐one 3a – k and isonicotinic acid hydrazide in the presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in‐vitro antibacterial activity against Gram‐positive and Gram‐negative bacteria. Among the series, compounds 4e , 4i , and 4k displayed an encouraging antibacterial activity profile as compared to the reference drug ampicillin against tested bacterial strains.     

Synthesis and In Vitro Antibacterial Activity of 7‐(3‐Alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)‐fluoroquinolone Derivatives

A series of novel 7‐(3‐alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)fluoroquinolone derivatives were designed, synthesized, and characterized by ¹H‐NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in‐vitro antibacterial activity against representative Gram‐positive and Gram‐negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin‐sensitive Staphylococcus aureus (MSSA) and methicillin‐resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 μg/mL). In particular, compounds 14 , 19 , 28 , and 29 are fourfold more potent than ciprofloxacin against MSSA 08‐49. Compounds 23 , 26 , and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 μg/mL) against Acinetobactes calcoaceticus, which is two‐ to 16‐fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin.     

Synthesis and Antimicrobial Activity of 4‐Chloro‐3‐Nitrophenylthiourea Derivatives Targeting Bacterial Type II Topoisomerases

A series of novel 4‐chloro‐3‐nitrophenylthiourea derivatives were synthesized and evaluated for their antimicrobial, antibiofilm and tuberculostatic activities. Most of compounds exhibited high antibacterial activity against both standard and hospital strains (MIC values 0.5–2 μg/mL), as compared to Ciprofloxacin. Derivatives with 3,4‐dichlorophenyl ( 11 ) and 3‐chloro‐4‐methylphenyl ( 13 ) substituents were the most promising towards Gram‐positive pathogens. Both of them exhibited antibiofilm potency and effectively inhibited the formation of biofilms of methicillin‐resistant and standard strains of Staphylococcus epidermidis. Two N‐alkylthioureas ( 20, 21 ) showed twofold to fourfold increase in in vitro potency against isolates of Mycobacterium tuberculosis, as compared to Isoniazid. An action of 7, 10 , 11, 13, 20 and 21 against activity of topoisomerases isolated from Staphylococcus aureus was studied. Synthesized compounds were found as non‐genotoxic.     

Synthesis and Antibacterial Activity of a Novel Series of 2,3‐Diaryl‐substituted‐imidazo(2,1‐b)‐benzothiazole Derivatives

Benzothiazole and imidazole compounds are extensively studied heterocyclics due to their wide spectrum of bioactivities. Among them, the imidazo(2,1‐b)‐benzothiazole derivatives are pharmacologically important because of their immunostimulant, anti‐inflammatory, antifungal, antimicrobial, antitumor, and other activities. In the present research work, a novel series of 2,3‐diaryl‐substituted imidazo(2,1‐b)‐benzothiazoles 13a–o have been synthesized by reaction of substituted 2‐aminobenzothiazoles 1–8 and an appropriately substituted α‐bromo‐1‐(4′′‐substituted)‐phenyl‐2‐(4′‐substituted)‐phenyl‐1‐ethanones 9–12 in the presence of anhydrous acetonitrile. They were characterized by physicochemical, elemental, and spectral (IR, ¹H‐NMR, and Mass) data. All the synthesized compounds were screened for their in‐vitro antibacterial activity against Gram‐positive, Gram‐negative bacteria. The investigation of antibacterial screening data revealed that most of the compounds tested have demonstrated congruent activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa as compared with the standard ampicillin. Among the series, compounds 13d , 13h , and 13m exhibited excellent an antibacterial activity profile as compared with the standard. In summary, preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activities and they warrant more consideration as prospective antimicrobials.     

Synthesis and Antitubercular Activity of 2‐(substituted phenyl/benzyl‐amino)‐6‐(4‐chlorophenyl)‐5‐(methoxycarbonyl)‐4‐methyl‐3,6‐dihydropyrimidin‐1‐ium Chlorides

A series of 2‐(substituted phenyl/benzyl‐amino)‐6‐(4‐chlorophenyl)‐5‐(methoxycarbonyl)‐4‐methyl‐3,6‐dihydropyrimidin‐1‐ium chlorides 7–13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT‐IR, NMR (¹H and ¹³C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 μg/mL against multidrug resistance tuberculosis and over 64 μg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X‐ray study.     

Design,Synthesis, Antibacterial Evaluation and Docking Study of Novel 2‐Hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived Quinolone

A novel series of 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived quinolones 6a – o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram‐positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram‐positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl group formed two additional hydrogen bonds.     

Synthesis and Antimicrobial Activity of Some Novel 2‐[4‐(Substituted Piperazin‐/Piperidin‐1‐ylcarbonyl)phenyl]‐1H‐benzimidazole Derivatives

In this study, we report the synthesis and antimicrobial evaluation of several new 4‐(1H‐benzimidazol‐2‐yl)benzamides ( 11 – 30 ) and 5‐chloro‐1‐(p‐fluorobenzyl)‐2‐{4‐[(4‐methylpiperazin‐1‐yl)carbonyl]phenyl}‐1H‐benzimidazole ( 33 ). Compound 20 exhibited the best antibacterial activity with MIC value of 6.25 μg/mL against Staphylococcus aureus and methicillin‐resistant Staphylococcus aureus (MRSA). Significant antifungal activities were obtained with the compounds 13 , 14, 18 , 19, and 33 with MIC values of 3.12 μg/mL which are close to fluconazole.     

Design,synthesis, and in vitro antimicrobial activity of hydrazide–hydrazones of 2‐substituted acetic acid

In this study, 30 hydrazide–hydrazones of phenylacetic ( 3 – 10 ) and hydroxyacetic acid ( 11 – 32 ) were synthesized by the condensation reaction of appropriate 2‐substituted acetic acid hydrazide with different aromatic aldehydes. The obtained compounds were characterized by spectral data and evaluated in vitro for their potential antimicrobial activities against a panel of reference strains of micro‐organisms, including Gram‐positive bacteria, Gram‐negative bacteria, and fungi belonging to the Candida spp. The results from our antimicrobial assays indicated that among synthesized compounds 3 – 32 , especially compounds 6 , 14, and 26 showed high bactericidal activity (MIC = 0.488–7.81 μg/ml) against reference Gram‐positive bacteria, and in some cases, their activity was even better than that of commonly used antibiotics, such as cefuroxime or ampicillin.     

4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5-fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial screening

As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7‐fluoro‐3,4‐dihydro‐2H‐1,4‐benzothiazine derivatives ( 4a–4f , 4h ) and 7‐fluoro‐2H‐1,4‐benzothiazin‐3(4H)‐one analogues ( 4j–4o ) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram‐positive and Gram‐negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro‐substituted‐2‐amino‐5‐fluorobenzenethiol 6a–6c . The biological screening identified in compounds 4a , 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a–6c . Surprisingly, 6a–6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram‐positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents.     

Novel Cationic Quinazolin‐4(3H)‐one Conjugated Fullerene Nanoparticles as Antimycobacterial and Antimicrobial Agents

A series of novel cationic fullerene derivatives bearing a substituted‐quinazolin‐4(3H)‐one moiety as a side arm were synthesized using the 1,3‐dipolar cycloaddition reaction of C₆₀ with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinones. The synthesized compounds 5a – f were characterized by elemental analysis, FT‐IR, ¹H NMR, ¹³C NMR, and ESI‐MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H₃₇RV) and antimicrobial activity against selected Gram‐positive (Staphylococcus aureus and S. pyogenes) and Gram‐negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial and fungal strains (Candida albicans, Aspergillus clavatus, and A. niger), respectively. All the compounds exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs.     

Synthesis and Antimicrobial Activities of a Novel Series of Heterocyclic α‐Aminophosphonates

Two series of novel α‐aminophosphonates having heterocyclic moieties were synthesized in high yields. The structures of the newly synthesized compounds were confirmed by their elemental analyses, IR, ¹H NMR and MS spectral data. These compounds were screened for their antibacterial activities against Escherichia coli (NCIM2065) as a Gram‐negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram‐positive bacteria, and Candida albicans and Saccharomyces cerevisiae as fungi. The minimum inhibitory concentrations (MICs) of the synthesized compounds show high antibacterial and antifungal activities at low concentrations (10–1000 µg/mL). Furthermore, their lethal doses indicated that such compounds are safe for use as antimicrobial agents.     

6‐Substituted Indolo[1,2‐c]quinazolines as New Antimicrobial Agents

A series of 2‐o‐arylidineaminophenylindoles and their cyclic derivatives (indolo[1,2‐c]quinazolines) were synthesized. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. Molecular structures of the synthesized compounds were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, MS spectra, and elemental analyses. Furthermore, all the final products were screened for in‐vitro antibacterial activity against three Gram‐positive and three Gram‐negative bacteria and also tested for their inhibitory action against three strains of fungi. Compound IIc showed potent activity against all the bacterial (except S. typhimurium) and fungal strains. Especially, compounds IIi and IIj which have isoquinolyl and pyridyl substituents displayed potent antibacterial as well as antifungal activities compared to those of the respective standard drugs Ampicillin and Ketoconazole.     

Synthesis and Antibacterial Activity of a Series of α‐Substituted Acetylpiperazinyl Oxazolidinones

A series of oxazolidinone derivatives with α‐substituted acetylpiperazinyl groups were prepared. Their in vitro antibacterial activities were studied against Gram‐positive pathogens, including methicillin‐resistant Staphylococcus aureus, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. The compounds with chloroacetyl‐piperazinyl or dichloroacetyl‐piperazinyl group were found to have superior antibacterial activities to linezolid against most of tested Gram‐positive pathogens. The compounds with propionylpiperaziny or fluoroacetylpiperazinyl group were found to have comparable antibacterial activities with linezolid. However, the replacement of phenyl ring of the compounds with pyridine ring resulted in the significant loss of antibacterial activity.     

Efficient Synthesis and Biological Evaluation of a Novel Series of 1,5‐Benzodiazepine Derivatives as Potential Antimicrobial Agents

A series of novel 1,5‐benzodiazepine derivatives were rationally designed and synthesized following the principle of the superposition of bioactive substructures by the combination of 1,5‐benzodiazepine, pyridine (phenyl), and an ester group. The structures of the target compounds were determined by ¹H NMR, ¹³C NMR, MS, IR, and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi C. neoformans, C. neoformans clinical isolates (ATCC 32264), C. albicans (ATCC 10231), Gram‐negative bacterium E. coli (ATCC 44752), and Gram‐positive bacterium S. aureus (ATCC 25923). The results of the bioactive assay demonstrated that most of the tested compounds exhibited variable inhibitory effects on the growth of the tested microorganisms. All the active compounds showed better antifungal activity than antibacterial activity. Notably, compound 2b displayed the highest activity (MIC = 30 μg/mL) against C. neoformans and (MIC = 31 μg/mL) against C. neoformans clinical isolates. In addition, compound 2a also showed excellent activity against C. neoformans and C. neoformans clinical isolates with minimum inhibitory concentration of 35 and 36 μg/mL, respectively. Compounds 2a and 2b were further studied by evaluating their cytotoxicities, and the results showed that they have relatively low level cytotoxicity for BV2 and 293T cell. Preliminary structure‐activity relationship study on three diverse sets (C‐2, C‐3, and C‐8 positions) of 1,5‐benzodiazepines was performed. The results revealed that the presence of a ‐CH₃ group at the C‐8 position had a positive effect on the inhibitory activity of these compounds. Additionally, the 2‐pyridyl group at the C‐2 position may be a pharmacophore and ‐COOC₂H₅ at C‐3 position is the best substituent for the maintenance of antimicrobial activities.     

Scalable synthesis and antibacterial evaluation of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles

A new series of 2‐(3‐(N‐(substituted phenyl)sulfamoyl)ureido)benzothiazoles was synthesized via a one‐pot efficient and scalable method, involving the condensation of 2‐aminobenzothiazoles derivatives, substituted anilines, and chlorosulfonyl isocyanate. The products were obtained in good yield with a simple workup, and their structures were confirmed from their spectral analyses. The synthesized compounds were further screened for their antibacterial activity against Gram‐positive and Gram‐negative pathogenic strains. The molecules show promising activity in the MIC value range of 2–0.25 µg/ml against selected bacterial strains, especially against nonfermentative carbapenem‐resistant bacteria (Pseudo VIM‐2 and Acinetobacter baumanni).     

Synthesis and anti‐Candida activity of novel benzothiepino[3,2‐c]pyridine derivatives

A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C. parapsilosis (clinical isolate), Gram‐negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram‐positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8‐phenyl[1]benzothiepino[3,2‐c]pyridine ( 16 ) efficiently killed Candida albicans at 15.6 μg/mL and showed no embryotoxicity at 75 μg/mL. Derivative 8‐[4‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)phenyl][1]benzothiepino[3,2‐c]pyridine ( 23 ) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.     

Synthesis,characterization, and antimicrobial activity of some new N‐aryl‐N’‐(2‐oxoindolin‐3‐ylidene)‐benzohydrazonamides

A green approach was developed for synthesizing a series of (isatin‐3‐ylidene)‐hydrazonamides 3a–j  from the reaction between isatin, (isatin‐3‐ylidene)malononitrile, or 2‐cyano‐2‐(2‐isatin‐3‐ylidene)acetate and benzohydrazonamide in ethyl acetate solutions at ambient temperature. The structures of the new compounds were confirmed on the basis of spectral data. In this eco‐friendly medium, a variety of (isatin‐3‐ylidene)hydrazonamides were obtained free of catalyst in good to excellent yields. All the synthesized products were evaluated for their antimicrobial activity. Among the compounds tested, 3b and 3d exhibited good antibacterial activity against Staphylococcus aureus, whereas others responded moderately with reference to the standard drug ciprofloxacin.     

Synthesis and In Vitro Antibacterial Activity of (2S)‐N‐(Substitutedphenyl)‐1‐[(2R)‐2‐[(Formylhydroxyamino)Methyl]‐1‐Oxohexyl]‐2‐Pyrrolidinecarboxamides as Potential Peptide Deformylase Inhibitors

Gram‐positive organisms have re‐emerged as the major hospital pathogens, which make the unmet medical needs for antibacterial therapy even worse. In searching for potent agents against Gram‐positive pathogens, novel (2S)‐N‐(substitutedphenyl)‐1‐[(2R)‐2‐[(formylhydroxyamino)methyl]‐1‐oxohexyl]‐2‐pyrrolidinecarboxamides, analogues of peptide deformylase inhibitor LBM‐415 were designed, synthesized and evaluated for their antibacterial activities in vitro. Many of these compounds exhibited high potency against Gram‐positive organisms compared with reference agent: LBM‐415.     

Synthesis of New N‐Substituted 5‐Arylidene‐2,4‐thiazolidinediones as Anti‐Inflammatory and Antimicrobial Agents

A novel series of 5‐arylidene ‐ 2,4‐thiazolidinediones (TZDs) 2a – p was synthesized from the condensation of 3‐((2‐phenylthiazol‐4‐yl)methyl)thiazolidine‐2,4‐dione with different benzaldehyde derivatives. All the structures were confirmed by their spectral (IR, ¹H NMR, ¹³C NMR and mass) and elemental analytical data. The new molecules were evaluated in vivo as anti‐inflammatory agents in an acute experimental inflammation, evaluating the acute phase bone marrow response and phagocyte activity. All compounds, excepting one, reduced the absolute leukocytes count due to the lower neutrophil percentage. Phagocytary index was decreased by the same molecules, while only half of them reduced the phagocytary activity. The effect was superior to meloxicam, the reference anti‐inflammatory drug, for the majority of the TZD derivatives. The new molecules were also investigated for their antimicrobial properties on Gram‐positive and Gram‐negative bacteria and one fungal strain. Two compounds ( 2e and 2n ) manifested growth inhibition capacity on all the tested strains.     

Study of the Cytotoxic and Bactericidal Effects of Sila‐substituted Thioalkyne and Mercapto‐thione Compounds based on 1,2,3‐Triazole Scaffold

A series of sila‐organosulphur compounds containing 1,2,3‐triazole cores were screened for their cytotoxic activity on human breast cancer cell line MCF‐7. Most of the tested compounds exhibited moderate‐to‐good activity against the cancer cells. Especially, the compound 4‐((2‐(trimethylsilyl)ethynylthio)methyl)‐1‐benzyl‐1H‐1,2,3‐triazole ( 3a) from series of sila‐substituted thioalkyne 1,2,3‐triazoles (STATs) and the compounds 3‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐mercapto‐1,1‐bis(trimethylsilyl)propane‐2‐thione ( 4a) and 1‐mercapto‐1,1‐bis(trimethylsilyl)‐3‐(1‐phenethyl‐1H‐1,2,3‐triazol‐4‐yl)propane‐2‐thione ( 4e) from series of sila‐substituted mercapto‐thione 1,2,3‐triazoles (SMTTs) exhibited promising cytotoxicity against MCF‐7 with IC₅₀ values of 35.17, 32.63 and 30.3 μg/mL, respectively. In addition, the possible mechanisms for inhibition of cell growth and induction of apoptotic cell death were explored by DAPI staining, cell cycle analysis and qRT‐PCR. The synthetic compounds were evaluated for their in vitro antibacterial activities, and as a result, the most prominent effects were observed for 3e and 4e . Especially, 3e was found to be quite active against all the tested strains with the MIC values ranging from 15 to 62 μg/mL, except P. aeruginosa. The results of the time‐kill assay suggested that the compound of 3e completely inhibited the growth of both gram‐negative bacteria, A. baumannii, and gram‐positive bacteria, S. aureus. In addition, SEM analysis confirmed morphostructural damage of the bacteria. Our findings could be applicable for developing dual‐targeting anticancer/antibacterial therapeutics.