Design,synthesis, antimicrobial evaluations and in silico studies of novel pyrazol-5(4H)-one and 1H-pyrazol-5-ol derivatives

A new series of 1,4-disubstituted 3-methylpyrazol-5(4H)-one derivatives were synthesized by reacting various substituted aromatic aldehydes with 3-methylpyrazol-5(4H)-one derivatives through Knoevenagel condensation by conventional as well as by exposure to microwave irradiations. After that newly synthesized compounds of 1,4-disubstituted 3-methyl-1H-pyrazol-5-ol were prepared from these derivatives by reduction reaction of sodium borohydride at 0–5 °C. Sixty-four heterocyclic compounds containing a pyrazole moiety were synthesized with good to excellent yields (51 to 91%). Compounds (3d, 3m, 4a, 4b, 4d, and 4g) showed potent antibacterial activity against MSSA (Methicillin-susceptible strains of Staphylococcus aureus) and MRSA (Methicillin-resistant strains of Staphylococcus aureus) with MIC (the minimum inhibitory concentration) ranging between 4 and 16 µg/mL as compared to ciprofloxacin (MIC = 8–16 µg/mL). Compounds (4a, 4h, 4i, and 4l) showed potent antifungal activity against Aspergillus niger with MIC ranging between 16 and 32 µg/mL as compared to fluconazole (MIC = 128 µg/mL). In particular, compound 4a exhibited the strongest activity among the synthesized compounds in both bacterial and fungal strains with MIC ranging between 4 and 16 µg/mL. Furthermore, the nine most active compounds showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile in comparison to ciprofloxacin and fluconazole as reference drugs. Molecular docking predicted that DHFR (dihydrofolate reductase) protein from Staphylococcus aureus and NMT (N-myristoyl transferase) protein from Candida albicans are the most suitable targets for the antimicrobial activities of these potent compounds.     

Molecular modeling and docking studies of new antimicrobial antipyrine-thiazole hybrids

A series of new antipyrine incorporated thiazole derivatives having phenoxyacetamide moiety as a link bridge was synthesized. The synthetic strategy involves condensation of the precursor N-(4-antipyrinyl)-2-(4-formylphenoxy)acetamide with thiosemicarbazide followed by heterocyclization of the produced thiosemicarbazone with various α-halogenated carbonyl compounds (namely; 4-chlorophenacyl bromide, ethyl bromoacetate, 3-chloroacetylacetone and ethyl 4-chloroacetoacetate). Moreover, the quantum chemical calculations at DFT/B3LYP level were used to determine the HOMO-LUMO energies and Fukui’s indices toward nucleophilic, electrophilic and radical attacks. The investigated compounds were arranged due to HOMO-LUMO energy gap as following 6 < 5 < 7 < 3 < 2 < 4 < 8. The synthesized antipyrinyl-thiazole hybrids were screened to evaluate their antibacterial and antifungal efficacies. Using Chloramphenicol as reference material, the synthesized antipyrinyl-thiazole hybrids were revealed a remarkable activity against S. aureus than B. subtilis, as example for Gram’s positive strains. The antipyrine-thiazole compounds 3, 4, 6 and 8 exhibited significant MIC values. However, the antipyrine-thiazole hybride 4 displayed reputable activities against Gram’s negative strains S. typhimurium and E. coli, respectively, in comparison with Cephalothin. Likewise, the compounds 7 and 8 were demonstrated respectable antifungal efficacy toward C. albicans in contrast to cycloheximide grade. The theoretical molecular docking studies were applied to simulate reactivity of the synthesized antipyrine-thiazole hybrids against contrasting binding sites for both of Staphylococcus aureus “Homo sapiens” (pdb: 3HUN) protein and E.coli “Homo sapiens” (PDB: 2EXB) protein. The theoretical and practical antibacterial and antifungal activities result in this work designated a proper agreement.     

Synthesis and biological evaluation of 1,4-pentadien-3-one derivatives containing 1,2,4-triazole

A series of new 1,4-pentadien-3-one derivatives containing 1,2,4-triazole moiety were synthesized. The structures of the synthesized compounds were charactered via ¹H NMR, ¹³C NMR and HRMS. Antibacterial bioassays indicated that some of compounds showed potential antibacterial activities against Ralstonia solanacearum (Rs), Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri (Xac). Compounds F₈ and F₁₇ showed good in vitro antibacterial activities against Rs, with the EC₅₀ values of 18.6 and 18.6 μg/mL, respectively, which were better than commercial agent bismerthiazol (55.2 μg/mL). Furthermore, compounds F₁₂ and F₁₅ showed good in vitro antibacterial activities against Xoo, with the EC₅₀ values of 10.9 and 17.5 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Moreover, compounds F₂, F₉, F₁₆ and F₁₇ showed good in vitro antibacterial activities against Xac, with the EC₅₀ values of 6.6, 5.4, 7.5 and 7.8 μg/mL, respectively, which were better than commercial agent bismerthiazol (54.9 μg/mL). The effect of compound F₉ on Xac bacterial cell membrane rupture was observed by scanning electron microscopy (SEM). In addition, antiviral bioassays indicated that some of compounds showed excellent protection activities against tobacco mosaic virus (TMV). Compounds F₅ and F₁₅ showed good protecting activity against TMV, with the EC₅₀ values of 108.3 and 105.4 μg/mL, respectively, which were better than commercial agent ningnanmycin (214.7 μg/mL). Microscale thermophoresis (MST) also showed that the binding of compound F₂ to TMV coat protein (TMV-CP) yielded a Kd value of 1.260 ± 0.654 μmol/L, which was very close to ningnanmycin (1.058 ± 0.286 μmol/L). Similarly, the molecular docking studies for F₂ and F₅ with TMV-CP (PDB code: 1EI7, ID: 4QGH) indicated that compounds F₂ and F₅ had partially interacted with TMV-CP.     

Synthesis of some Mannich base derivatives and their antimicrobial activity study

A series of 2-(phenyl)-2-(morpholin-4-yl)-N-phenylacetamide I–VII were synthesized by Mannich base method. Synthesized compounds I–VII were confirmed by IR, ¹H NMR, ¹³C NMR, mass and elemental analyses. Synthesized compounds I–VII were screened for antibacterial activity against various bacterial strains and compared with standard Ciprofloxacin at concentration 100 μg/mL and for antifungal activity against various fungal strains and compared with Clotrimazole at concentration 100 μg/mL; particularly 3-(4-chlorophenyl)-3-(morp holin-4-yl)-N-phenylpropanamide lll that has high antibacterial activity against Streptococcus epidermidis was compared with standard Ciprofloxacin.     

Design,synthesis, characterization,and antimicrobial evaluation of some new pyridine and chromene derivatives containing Lidocaine analogue

In an attempt to find a new class of antimicrobial agents, a series 2-pyridinone and 2-iminochromene derivatives containing Lidocaine analogue were designed and synthesized. The 2-pyridinone derivatives (3), (4), and (6) were obtained through the cyclocondensation of 2-cyano-N-(2,6-dimethylphenyl)-acetamide (2) with 1,3-dicarbonyl compounds and/or ternary condensation of (2), aromatic aldehyde, and malononitrile. Also, a series of 2-iminochromene derivatives (7–9) were synthesized through the condensation reaction of cyanoacetamide derivative (2) with salicylaldehyde derivatives. The structure of the new compounds were confirmed based on elemental analysis and spectral data. These compounds were screened for their antibacterial and antifungal activity The minimal inhibitory concentration (MIC) (µg/mL) of the most active (4), (5b), and (8) derivatives were determined. The MIC values between 7.81 and 31.26 µg/mL against bacterial species for (8) derivative, and upon comparison to tetracycline exhibited a positive control MIC (31.26–62.6 µg/mL). Besides, the activity against C. albicans (ATCC 1023) showed a MIC value of 15.63 µg/mL, which is similar to that of Amphotericin B.     

Synthesis,biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

A series of 8-(substituted)aryloxycaffeine were prepared from 8-bromocaffeine and (substituted)phenols by modified Ullmann reaction. In vitro antibacterial activity, inhibitory activity on topoisomerase II and pharmacological activities were evaluated for the synthesized 8-(substituted)aryloxycaffeine. Among the synthesized compounds, 8-(5-chloropyridin-3-yloxy)caffeine (3k) showed strong inhibitory activity (MIC = 15.6 μg/mL) against the tested gram negative (−) bacteria Salmonella enteritidis. 8-(quinolin-8-yloxy)caffeine (3g) showed the strongest inhibitory activity against topoisomerase II. And the compounds 8-(6-methylpyridin-2-yloxy)caffeine (3j) and 8-(3-chloro-6-(trifluoromethyl)pyridin-2-yloxy)caffeine (3m) showed analgesic effect without the central nervous system stimulation.     

Design,synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

Increase in the number of infections caused by pathogenic microbes in cancer patients has prompted the searcher to invest in the development of agents having dual anticancer and antimicrobial properties. The present study is concerned with synthesis and screening for anticancer and antimicrobial activity of a series of 5-hydrazinyl-2-(2-(1-(thien-2-yl)ethylidene)hydrazinyl)thiazole derivatives. The structure elucidation of the synthesized hydrazinyl thiazole derivatives was illustrated by spectroscopic and elemental analysis. All the newly synthesized compounds 5a-p were evaluated for in-vitro cytotoxic activity against breast carcinoma (MCF-7 cell line), hepatocellular carcinoma (HePG-2) and colorectal cancer (HCT-116) cell lines using MTT assay method. Compounds 5 g, 5h showed broad spectrum activity against three cancer cell lines with IC₅₀ ranged from 3.81 to 11.34 µM in compared to the reference drug Roscovitine (IC₅₀ = 9.32 to 13.82 µM), while compounds 5 l and 5 m were found to be more selective against HePG-2 and HCT-116 cell line (IC₅₀ = 9.29 and 8.93 µM respectively) and compound 5j was more selective against HePG-2 and MCF-7 cell lines (IC₅₀ = 6.73 and 10.87 µM respectively). The inhibitory activity of the most promising compounds was tested against the EGFR and ARO enzymes and were further tested for apoptosis and Annexin V/PI staining. The results of enzyme-based tests revealed that the tested compound 5j has a dual inhibitory effect on the EGFR and ARO enzymes with IC₅₀ = 82.8 and 98.6 nM respectively in compared to the reference drugs Erlotinib and Letrozole (IC₅₀ = 62.4 and 79 nM respectively). Furthermore, the majority of the tested hydrazinyl thiazole derivatives exhibited significant antimicrobial activity against the used pathogenic microbes species. Compounds 4b, 5h, 5j and 5 m exerted a good antibacterial and antifungal activity against all tested pathogenic microbes. Therefore, it was concluded that compounds 5 h, 5j and 5 m proved to possess dual anticancer and antimicrobial agent and may serves as a useful lead compounds in search for further modification or derivatization to give more potent and selective agents.     

Synthesis and pharmacological evaluation of 9(10H)-acridone bearing 1,3,4-oxadiazole derivatives as antimicrobial agents

In the present study a new acridone derivatives were synthesized. The newly synthesized compounds were characterized by IR, NMR and C, H, N, S analyses. All newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Streptococcus viridans and Escherichia coil) and antifungal (Gibberela, Cercospora arachidicola, Physolospora piricola and Fusarium oxysporum) studies. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms.     

Synthesis,antimicrobial activity and docking study of some novel 4-(4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino derivatives carrying biologically active sulfonamide moiety

A new series of 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(substituted)benzenesulfonamide 3–17, monosubstituted 2-((4-((4-aminophenyl)sulfonyl)phenyl)amino)methylene 18, and its disubstituted derivative 19 were synthesized from the starting material 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione 2. The crystal structures of compounds 2, 7 and 13 were reported by us through X-ray crystallography. All the prepared compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans. The synthesized compounds displayed interesting antimicrobial activity. Compounds 4 and 12 were the most potent in this study and displayed higher activity compared to the reference drugs, with MIC value of 3.9–31.3 μg/mL against a panel of Gram-positive, Gram-negative bacteria and fungi. Molecular modeling was performed inside the active site of dihydropteroate synthase. The synthesized compounds showed similar orientation and binding interactions to that of the co-crystallized ligand inside the binding pocket.     

Synthesis of 5-{[(1Hbenzo[d]imidazol-2-yl)sulfonyl]methyl}-3-phenyl-4,5-dihydroisoxazole derivatives,invitro antibacterial and antioxidant studies along with their insilico analyses

Synthesis of a series of novel sulfone derivatives 6(a-u) possessing benzimidazoles and isoxazoline rings tailored in a single molecule 5(a-u) was done by reactions using 5-(bromomethyl)-3-phenyl-4,5-dihydroisoxazoles 3(a-u) and 5-{[(1H-benzo[d]imidazol-2-yl)thio]methyl}-3-phenyl-4,5-dihydroisoxazoles 4(a-u) molecules. The chemical structures of all the newly synthesized compounds were established by IR, ¹HNMR, ¹³CNMR and LCMS spectral data. The biological characteristics of the novel sulfone compounds, such as their antioxidant and antibacterial activity, were evaluated. Among the synthesized sulfones derivatives, compounds 6 g, 6b, and 6e demonstrated outstanding antibacterial activity while compounds 6b, 6c, 6i, 6j, and 6 k demonstrated higher antioxidant activity. Further insilico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies of synthesized sulfones were studied which exhibited excellent intestinal absorption which is more than 80 %, and relatively moderate toxicity. Molecular docking studies confirmed the antibacterial and antioxidant potential which is comparable with the standard.     

Synthesis,in-silico antiviral screening and in-vitro antibacterial screening of a novel chalcone derivatives

A new series of novel chalcones was synthesized and subjected to screening of theoretical molecular and biological properties. For evaluating the theoretical molecular properties of these molecules Molinspiration and Osiris software were used. It was concluded from data that the majority of molecules exhibited theoretical molecular and biological properties similar to that of standard drugs. Role of Hemagglutinin is vital during the attack of virus on cells so Hemagglutinin inhibitors may act as potent antiviral agents. Considering this fact in-silico studies were performed using the SwissDock screening engine on Hemagglutinin target PDB code 1HGH. Hemagglutinin inhibition potential in terms of binding affinity was expressed as ΔG values ranging from −8.71 kcal/mol to −7.39 kcal/mol. Compound IIIm showed maximum binding affinity with ΔG value −8.71 kcal/mol followed by compound IIIj ΔG value −8.31 kcal/mol. It's prudent from ΔG values that compounds may act as potent antiviral agents. Compounds were also screened for in-vitro antibacterial activity against five pathogenic strains. Most of the compounds exhibited low to moderate activity against strains under study. Compound IIIn demonstrated good activity against four pathogenic strains with highest zone of inhibition of 16 mm against K. pneumoniae and S. typhi.     

Design,synthesis and biological evaluation of novel 3-phenylpropanamide derivatives with acyl hydrazone units

In this study, a series of 3-phenylpropanamide derivatives with acyl hydrazone units were synthesized and characterized by ¹H NMR, ¹³C NMR and HR MS. And the structure of compound III₃₃ was confirmed by X-ray single crystal. The bioassay results showed that, compounds III₈, III₁₇, III₂₂, and III₃₄ showed excellent inhibition on Xanthomonas oryzae pv. pryzae (Xoo) with EC₅₀ values of 7.1, 8.8, 9.5, and 4.7 μg/mL in vitro. The EC₅₀ values of compounds III₁₂, III₁₄ and III₃₃ against Ralstonia solanacearum (Rs) were 7.6, 7.6 and 7.9 μg/mL, respectively, all lower than the values of thiadiazol copper (TC) was 66.8 μg/mL and bismerthiazol (BT) was 72.4 μg/mL. Compounds III₁₂, III₁₄, III₃₃, and III₃₄ exhibited excellent antibacterial activity of more than 80% against Xanthomonas axonopodis pv. citri (Xac) in vitro. Besides, compounds III₈ (51.4%) and III₃₄ (52.1%) were highly effective against Xoo in vivo, outperforming TC (49.5%) and BT (47.8%). Compounds III₈ (29.8%) and III₃₄ (24.6%) were close to TC (41.7%) and BT (47.8%) in terms of protective efficacy against Xoo in vivo. Meanwhile, some of title compounds also displayed inhibitory effects against phytopathogenic fungi. In a word, this study illustrated that the structures combined with phenylpropane amide derivatives of the acyl hydrazone units could be used as potential antibacterial reagents in the future.     

Multistep synthesis and screening of heterocyclic tetrads containing furan,pyrazoline, thiazole and triazole (or oxadiazole) as antimicrobial and anticancer agents

In the present study novel heterocyclic tetrads containing furan, pyrazoline, thiazole and triazole (or oxadiazole) (1, 2, 3, 4a-e and 5a-e) were designed and synthesized and investigated for their antimicrobial (against selected bacteria and fungi) and anticancer potential. The molecules 4e and 5e containing 4-fluoro phenyl and 4-fluoro benzyl substituents showed promising antimicrobial (antibacterial and antifungal activities with MICs ranging between 0.5 and 8 µg/mL. Compounds 3 exhibited potent anticancer activity with an IC₅₀ value of 0.49 ± 1.45 µM against the human gastric cancer cell line (BGC-823) whereas compound 4e displayed an IC₅₀ value of 0.65 ± 0.53 µM against breast cancer (MCF-7) cell line respectively. All compounds showed selective toxicity against the cancer cell lines compared to human normal liver cell lines. Molecular docking studies of the most potent compounds (3 and 4e) against selected microbial and cancer proteins revealed the crucial binding interactions of the potent compounds with the target enzymes. Compounds 3 and 4e are promising lead molecules to be developed as potential drug candidates.     

Synthesis,characterization and antibacterial activity of some new pyrazole based Schiff bases

In the present study a series of new Schiff bases were synthesized. All the synthesized compounds were characterized by IR, ¹H NMR, mass spectral and elemental analyses. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) activity. The results revealed that, compounds 3f and 3c have exhibited significant biological activity against the tested microorganisms.     

Molecular docking studies of some new imidazole derivatives for antimicrobial properties

In modern drug designing, molecular docking is routinely used for understanding drug-receptor interaction. In the present study six imidazole derivatives containing substituted pyrazole moiety (2a,b and 4a–d) were synthesized. Structures of the newly synthesized compounds were characterized by spectral studies. Compounds were screened for their antibacterial activity. Compound 4c was found to be potent antimicrobial against Pseudomonas aeruginosa at concentrations of 1 and 0.5 mg/mL compared to standard drug Streptomycin. All the compounds were subjected to molecular docking studies for the inhibition of the enzyme l-glutamine: d-fructose-6-phosphate amidotransferase[GlcN-6-P] (EC 2.6.1.16). The in silico molecular docking study results showed that, all the synthesized compounds having minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of GlcN-6-P synthase.     

One-pot multicomponent synthesis of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives and their biological evaluation as potential antioxidants,enzyme inhibitors,antimicrobials, cytotoxic and anti-inflammatory agents

A series of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives with substituted amine moieties (1–13) and substituted aldehyde (S) were designed and synthesized by a reflux condensation reaction in the presence of an acid catalyst to get N-Mannich bases. Mannich bases were evaluated pharmacologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cell cytotoxicity and anti-inflammatory activities. Most of the compounds exhibited potent activities against these bioassays. Among them, SH1 and SH13 showed potent antioxidant activity against DPPH free radical at IC₅₀ of 9.94 ± 0.16 µg/mL and 11.68 ± 0.32 µg/mL, respectively. SH7, SH10 and SH13 showed significant results in TAC and TRP antioxidant assays, comparable to that of ascorbic acid. SH2 and SH3 showed potent activity in inhibiting α-amylase enzyme at IC₅₀ of 10.17 ± 0.23 µg/mL and 9.48 ± 0.17 µg/mL, respectively, when compared with acarbose (13.52 ± 0.19 µg/mL). SH7 was the most active against gram-positive and gram-negative bacterial strains, SH13 being the most potent against P. aeruginosa by inhibiting its growth up to 80% (MIC = 11.11 µg/mL). SH4, SH5 and SH6 exhibited significant activity against some fungal strains. Among the thirteen synthesized compounds (SH1-SH13), four were screened out based on the results of brine shrimp lethality assay (LD₅₀) and cell cytotoxicity assay (IC₅₀), to determine their anti-cancer potential against Hep-G2 cells. The study was conducted for 24, 48, and 72 h. SH12 showed potent results at IC₅₀ of 6.48 µM at 72 h when compared with cisplatin (2.56 µM). An in vitro nitric oxide (NO) assay was performed to shortlist compounds for in vivo anti-inflammatory assay. Among shortlisted compounds, SH13 exhibited potent anti-inflammatory activity by decreasing the paw thickness to the maximum compared to the standard, acetylsalicylic acid (ASA).     

Pentacyclic Triterpenoids,Phytosteroids and Fatty Acid Isolated from the Stem-bark of Cola lateritia K. Schum. (Sterculiaceae) of Cameroon origin; Evaluation of Their Antibacterial Activity

The phytochemical investigation on the chemical constituents of dichloromethane-methanol (1:1) stem-bark extract of Cola lateritia K. Schum. (Sterculiaceae) led to the isolation and characterization of five pentacyclic triterpenoids, one fatty acid and two phytosteroids. The compounds were identified as heptadecanoic acid (1), maslinic acid (2), betulinic acid (3), lupenone (4), lupeol (5), friedelin (6), β-stigmasterol (7) and ß-sitosterol-3-O-ß-D-glucoside (8). Their structures were determined by NMR analysis (¹H, ¹³C, DEPT-135, COSY, HMBC and HSQC), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with published data in the literature. This work, to the best of our knowledge, is the first isolation and identification of these compounds in pure forms from Cola lateritia. Also, compounds 1–3 are reported for the first time from Cola genus. In vitro antibacterial activity of the isolated compounds (1–8) and the crude extract were evaluated against Bacillus subtilis, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium smegmatis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Proteus vulgaris, Klebsiella pneumonia, Escherichia coli, Proteus mirabilis and Klebsiella aerogenes with streptomycin, nalidixic acid and ampicillin as standard antibacterial drugs. Compound 2 was active against E. faecalis (MIC = 18.5 µg/mL), and it was 6.9 and 28 times lower and active than that of streptomycin (MIC 128 µg/mL) and nalidixic acid (MIC > 512 µg/mL) respectively. All the isolated compounds and crude extract showed significant activities against the tested bacterial strains.     

A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis,antimicrobial activity and molecular docking studies

A Novel class of 1,4-disubstituted 1,2,3-triazoles have been synthesized in good to excellent yields via Cu(I) accelerated azide-alkyne click chemistry reaction strategy. The newly synthesized compounds were assessed for their in vitro antimicrobial activity against five Gram-positive, seven Gram-negative bacteria and three fungi. Most of the synthesized compounds displayed significant activity against the tested Gram-positive and Gram-negative bacteria. Molecular docking study revealed that all docked compounds are bound efficiently with the active site of Topoisomerase IV (4EMV) receptor with the observed the free energy of binding from −7.79 to −9.44 kcal/mol. Interestingly, compound 13a forms four hydrogen bonds and displayed high binding energy (−9.44 kcal/mol) with the Topoisomerase IV (4EMV) receptor which correlated with their in vitro antimicrobial assays.     

Synthesis,characterization and antimicrobial activities of new bis-hydrazonothioxothiazolidinone derivatives

New bis-hydrazonothioxothiazolidinone derivatives based on 2-thioxothiazolidin-4-one were synthesized in good yields using a simplified experimental condition. The structure of synthesized compounds was established with the help of common physico-chemical analysis and various spectroscopic techniques like FT-IR, mass and ¹H NMR. The results of characterizations are in good agreement with the proposed structure of all the synthesized compounds. Further, the antimicrobial (antibacterial and antifungal) activities of all the synthesized derivatives were carried out against various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using agar-cup method. The results of antimicrobial screening showed that all the compounds have mild to moderate activity. However, some of the compounds (3a, 3b, 3d, 3e, 3f, 3g, 3i and 3j) have shown better activity than the other.