Aims: To synthesize novel sulfonamide inhibitors of carbonic anhydrase and develop in vitro prioritization workflow to select compounds for in vivo evaluation Background: Carbonic anhydrase (CA) inhibitors gain significant attention in the context of drug discovery research for glaucoma, hypoxic malignancies, and bacterial infections. In previous works, we have successfully used direct sulfochlorination approach to develop diverse heterocyclic primary sulfonamides with remarkable activity and selectivity against therapeutically relevant CA isoforms. Objective: Synthesis and investigation of the CA inhibitory properties of novel trifluoromethylisoxazolyl- and trifluoromethylpyrazolyl-substituted (hetero)aromatic sulfonamides. Methods: Thirteen trifluoromethylisoxazolyl- and thirteen trifluoromethylpyrazolyl-substituted (hetero)aromatic sulfonamides were synthesized by direct sulfochlorination of hydroxyisoxazolines and pyrazoles followed by reaction with ammonia. The compound structures were confirmed by 1 H and 13C NMR as well as element analysis. The obtained compounds were evaluated, using the CA esterase activity assay, for their potential to block the catalytic activity of bovine CA (bCA). Results: Eight most potent compounds selected based on the esterase activity assay data were tested for direct affinity to the enzyme using the thermal shift assay (TSA). These compounds displayed Kd values (measured by TSA) in the double-digit nanomolar range, thus showing comparable activity to the reference drug acetazolamide. Conclusion: Coupling the bCA esterase activity assay with thermal shift assay represents a streamlined and economical strategy for the prioritization of sulfonamide CA inhibitors for subsequent evaluation in vivo.

Background: A limited number of small molecules against SARS-CoV-2 has been discovered since the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial commitment, which is not achievable in the face of the current epidemic. Background: A limited number of small molecules against SARS-CoV-2 has been discovered since the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial commitment, which is not achievable in the face of the current epidemic. Objective: This study aims to discover and recognize the most effective and promising small molecules by interacting SARS-CoV-2 Mpro target through computational screening of 39 phytochemicals from five different Ayurveda medicinal plants. Methods: The phytochemicals were downloaded from PubChem, and the SARS-CoV-2 protein (PDB ID: 6LU7; Mpro) was taken from the PDB. The molecular interactions, binding energy, and ADMET properties were analyzed. Results: The binding affinities were studied using a structure-based drug design of molecular docking, divulging 21 molecules possessing greater to equal affinity towards the target than the reference standard. Molecular docking analysis identified 13 phytochemicals, sennoside-B (-9.5 kcal/mol), isotrilobine (-9.4 kcal/mol), trilobine (-9.0 kcal/mol), serratagenic acid (-8.1 kcal/mol), fistulin (-8.0 kcal/mol), friedelin (-7.9 kcal/mol), oleanolic acid (-7.9 kcal/mol), uncinatone (-7.8 kcal/mol), 3,4-di-O-caffeoylquinic acid (-7.4 kcal/mol), clemaphenol A (-7.3 kcal/mol), pectolinarigenin (-7.2 kcal/mol), leucocyanidin (-7.2 kcal/mol), and 28-acetyl botulin (-7.2 kcal/mol) from Ayurvedic medicinal plants phytochemicals possess greater affinity than (-7.0 kcal/mol) against SARS-CoV-2-Mpro. Conclusion: Two molecules, namely sennoside-B, and isotrilobine with low binding energies, were the most promising. Furthermore, we carried out molecular dynamics simulations for the sennoside-B protein complexes based on the docking score. ADMET properties prediction confirmed that the selected docked phytochemicals were optimal. These compounds can be investigated further and utilized as a parent core molecule to create novel lead molecules for preventing COVID-19. other: Not applicable

: Long-term exposure to pesticides is associated with the incidence of cancer. With the exponential increase in the number of new pesticides being synthesized, it becomes more and more important to evaluate the toxicity of pesticides by means of simulated calculations. Based on existing data, machine learning methods can train and model the predictions of the effects of novel pesticides, which have limited available data. Combined with other technologies, this can aid the synthesis of new pesticides with specific active structures, detect pesticide residues, and identify their tolerable exposure levels. This article mainly discusses support vector machines, linear discriminant analysis, decision trees, partial least squares, and algorithms based on feedforward neural networks in machine learning. It is envisaged that this article will provide scientists and users with a better understanding of machine learning and its application prospects in pesticide toxicity assessment.

: Calixarenes have always captured the attention of several researchers. They have the ability to entrap multiple molecules and form inclusion complexes with drugs due to their unique structure. Due to this property, they are being widely used in the development of several classes of drugs, most notably anticancer drugs. This review attempted to summarize the potential applications of calixarenes and its derivatives in the development of anticancer drugs, with a focus on the delivery of drug classes such as DNA intercalators, taxanes, DNA alkylators, and topoisomerase inhibitors. Calixarene-based macromolecular chemistry could therefore have a high potential for overcoming the toxicity of cancer chemotherapy and achieving targeted drug delivery.

Introduction: The nuclear transcription factor PPARγ, which can modulate cell growth via proliferation and apoptosis-related mechanisms, is a promising target in cancer therapy. This study aims to focus on PPARγ as the target and use virtual screening to find hits. Methods: A set of 5,677 flavonoid compounds were filtered by subjecting them to descriptor-based drug-likeness and ADMET strategies to discover drug-like compounds. The candidates' modes of binding to PPARγ were then evaluated using docking and MD simulation. PharmMapper was used to identify the potential targets of selected hits. The pharmacological network was constructed based on the GO and KEGG pathway analysis. Results: In primary screening, 3,057 compounds met various drug-likeness criteria and docked well as partial agonists in the PPARγ-LBD. Five compounds (euchrenone b1, kaempferol-7-Orhamnoside, vincetoxicoside B, morusin, and karanjin) were selected with the use of ADMET profiles for further MD simulation investigation. Based on the PharmMapper findings, 52 proteins were then submitted to GO and KEGG enrichment analysis. As expected by GO and KEGG pathway enrichment studies, core targets were enriched in the PI3K-Akt signaling pathway (p < 0.01), indicating that certain chemicals may be involved in cancer processes. Conclusion: Our results suggested that the selected compounds might have sufficient drug-likeness, pharmacokinetics, and in silico bioactivity by acting as PPARγ partial agonists. Although much work remains to illuminate extensive cancer therapeutic/ chemopreventive efficacy of flavonoids in vivo, in silico methodology of our cheminformatics research may be able to provide additional data regarding the efficacy and safety of potential candidates for therapeutic targets.

Background: KRAS and p53 are two of the most common genetic alterations associated with colorectal cancer. New drug development targeting these mutated genes in colorectal cancer may serve as a potential treatment avenue to the current regimen. Objective: The objective of the present study was to investigate the effects of alkoxy chain length and 1-hydroxy group on anticolorectal cancer activity of a series of 2-bromoalkoxyanthraquinones and corroborate it with their in silico properties. Methods: In vitro anticancer activity of 2-bromoalkoxyanthraquinones was evaluated against HCT116, HT29, and CCD841 CoN cell lines, respectively. Molecular docking was performed to understand the interactions of these compounds with putative p53 and KRAS targets (7B4N and 6P0Z). Results: 2-Bromoalkoxyanthraquinones with the 1-hydroxy group were proven to be more active than the corresponding counterparts in anticancer activity. Among the tested compounds, compound 6b with a C3 alkoxy chain exhibited the most promising antiproliferation activity against HCT116 cells (IC50 = 3.828 ± 0.05 µM) and showed high selectivity for HCT116 over CCD841 CoN cells (SI = 45.47). The molecular docking reveals additional hydrogen bonds between the 1-hydroxy group of 6b and the proteins. Compound 6b has adequate lipophilicity (cLogP = 3.27) and ligand efficiency metrics (LE = 0.34; LLE = 2.15) close to the proposed acceptable range for an initial hit. Conclusion: This work highlights the potential of the 1-hydroxy group and short alkoxy chain on anticolorectal cancer activity of 2-bromoalkoxyanthraquinones. Further optimisation may be warranted for compound 6b as a therapeutic agent against colorectal cancer. other: not applicable

: GPCR superfamily, the largest known family of membrane receptors, consists of six classes from A to F. GPR18 and GPR55, δ-branch of A class, had been reported to have no confirmed endogenous ligand and were named as “orphan receptors”. Previous studies suggest that both GPR18 and GPR55 are possibly related to the migration and proliferation of cancer cells, macrophages and other inflammation-associated immune cells. Thus, they may be potential targets for inflammation, cancer and analgesia therapy. In this paper, we aimed to summarize the chemical structures and bioactivities of the agonists and antagonists of GPR18 and GPR55; moreover, we have briefly discussed the challenges and future perspectives in this field. This review will be beneficial for further design and synthesis of efficient agonists and antagonists towards GPR18 and GPR55-related disease treatment.

Background: Berberine (BBR) is a quaternary ammonium alkaloid isolated from the Traditional Chinese Medicine Coptis chinensis. It possesses a plethora of pharmacological activities because its unique structure properties make it readily interact with macromolecules through π-π stacking and electrostatic interaction. Its anti-tumor effects are receiving more and more attention in recent years. Cytotoxicity and anti-proliferation are the important anti-tumor modes of BBR, which have been studied by many research groups. Objectives: This study aims to review the structural modifications of BBR and its cytotoxic derivatives. Also, to study the corresponding structure-activity relationship. BBR showed potential activities toward tumor cells, however, its modest activity and poor physicochemical properties hindered its application in clinical. Structural modification is a common and effective approach to improve BBR's cytotoxic or anti-proliferative activities. Results: The structural modifications of BBR, the cytotoxic or anti-proliferative activities of its derivatives, and the corresponding structure-activity relationship (SAR) were summarized in the review. Conclusion: The concluded SAR of BBR derivatives with their cytotoxic or anti-proliferative activities will provide great prospects for the future anti-tumor drug design with BBR as the lead compound.

Background: The prospective uses of tryptanthrin and its analogues in cancer chemotherapy are well known, and they are also predicated on their capacity to reverse drug resistance in cancer therapy. Objective: The current project entails developing a novel hybrid analogue that includes modifying the tryptanthrin molecule at the C-6 carbonyl position and is expected to exhibit substantial anticancer action. Method: In the ATPase domain of human topoisomerase II, a series of 162 substituted Schiff base analogues of tryptanthrin were developed, and molecular docking experiments were done using Gold 5.1 software interfaced with Hermes 1.6.2. (PDB ID: 1ZXM). Results: Most of the compounds were found to have Goldscore above 100 and were forming interactions with the residues like ASN91, ALA92, ASN95, ARG98, ASN120, ILE125, ILE141, PHE142, SER149, THR215, and ILE217. Compound RK-149 was having highest Goldscore of 132.59 forming an interaction with ASN91 but had lesser Goldscore as compared to standard drug etoposide and has better score than tryptanthrin. Conclusion: The nitrogen in the imine bond of the proposed compounds is responsible for significant interactions, demonstrating their anticancer potential.

Background: The severe acute respiratory syndrome coronavirus-2 is causing a disaster through coronavirus disease-19 (COVID-19), affecting the world population with a high mortality rate. Although numerous scientific efforts have been made, we do not have any specific drug for COVID-19 treatment. Objective: Aim of the present study was to analyse the molecular interaction of nitrogen heterocyclic based drugs (hydroxychloroquine, remdesivir and lomefloxacin) with various SARSCoV- 2 proteins (RdRp, PLPro, Mpro and spike proteins) using a molecular docking approach. Methods: We have performed docking study using PyRx software, and Discovery Studio Visualizer was used to visualise the molecular interactions. The designed nitrogen heterocyclic analogues were checked for Lipinski’s rule of five, Veber's Law and Adsorption, Distribution, Metabolism, and Excretion (ADME) threshold. After obtaining the docking results of existing nitrogen heterocyclic drugs, we modified the selected drugs to get molecules with better affinity against SARS-CoV-2. Results: Hydroxychloroquine bound to RdRp, spike protein, PLPro and Mpro at -5.2, -5.1, -6.7 and -6.0 kcal/mol, while remdesivir bound to RdRp, spike protein, PLPro, and Mpro at -6.1, -6.9, -6.4 and -6.9 kcal/mol, respectively. Lomefloxacin bound to RdRp, spike protein, PLPro and Pro at -6.4, -6.6, -7.2 and -6.9 kcal/mol. ADME studies of all these compounds indicated lipophilicity and high gastro intestine absorbability. The modified drug structures possess better binding efficacy towards at least one target than their parent compounds. Conclusion: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing the potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity

Excessive and uncontrolled oxidative stress can damage biomacromolecules, such as lipids, proteins, carbohydrates, and DNA, by free radical and oxidant overproduction. In this review, we critically discuss the main properties of free radicals, their implications in oxidative stress, and specific pathological conditions. In clinical medicine, oxidative stress can play a role in several chronic noncommunicable diseases, such as diabetes mellitus, cardiovascular, inflammatory, neurodegenerative diseases, and tumours. Antioxidant supplements can theoretically prevent or stop the progression of diseases, but a careful literature analysis finds that more evidence is needed to dissect the ultimate beneficial effect of antioxidants versus reactive oxygen species in several diseases.

: Quinoline and its analogues are found in various natural products, many of which are active pharmacophores with significant bioactivities. This article discussed the plethora of quinoline derivatives and their analogues that have anti-cancer properties. The review will be helpful for the scientific community since several possible anticancer drugs based on quinolines are discussed here. In addition to this, the synthetic aspect of many such quinoline derivatives showing anti-cancer activities is also revealed in this article. These quinoline-based anti-oncogenic molecules can be synthesized using several acids, bases, and azides or with the help of reagents like Jone’s reagent and Lawesson’s reagent.

Background: The carbonic anhydrases (CAs) which are found in most living organisms is a member of the zinc-containing metalloenzyme family. The abnormal levels and activities are frequently associated with various diseases therefore CAs have become an attractive target for the design of inhibitors or activators that can be used in the treatmentof those diseases. Methods: Herein, we have designed and synthesized new benzimidazole-hydrazone derivatives to investigate the effects of these synthesized compounds on CA isoenzymes. Chemical structures of synthesized compounds were confirmed by 1H NMR, 13C NMR, and HRMS. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by in vitro assay. Results: These compounds have IC50 values of 5.156-1.684 µM (hCA I) and 4.334-2.188 µM (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 5.44±0.14 µM-0.299±0.01 µM (hCA I) and 3.699±0.041 µM-1.507±0.01 µM (hCA II). The synthetic compounds displayed inhibitory action comparable to that of the clinically utilized reference substance, acetazolamide. According to this, compound 3p was the most effective molecule with an IC50 value of 1.684 µM. Accordingly, the type of inhibition was noncompetitive and the Ki value was 0.299±0.01 µM. Conclusion: According to the in vitro test results, detailed protein-ligand interactions of the compound 3p, which is more active against hCA I than standard azithromycin (AZM), were analyzed. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.

Severe emergencies occurred across the globe, beginning with the outbreak of SARSCoV in 2002, followed by MERS-CoV in 2012. In December 2019, an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China as the agent responsible for the recent COVID-19 pandemic outbreak. The virus rapidly spread throughout the world due to its high transmissibility, leading to enormous health problems and complexities. The COVID-19 pandemic has affected public health, the weak persons were severely affected by this virus. To stop the disease from spreading further, effective remedies are the need of the hour. Although SARS-CoV-2 vaccination campaigns are being carried out all over the globe, several new SARS-CoV-2 variants have emerged, and each has caused a wave of infections, highlighting an urgent need for therapeutics targeting SARS-CoV-2. Heterocyclic compounds have been explored extensively for a very long time for their biological activities, namely, anti-inflammatory, antimalarial, antitubercular, anticancer, antiviral, antimicrobial, antidiabetic, and many more bio-activities. Through this review, the author has tried to report the heterocyclic compounds synthesized all over the world over the last 2 years to fight against the SARS CoV-2 coronaviruses. The heterocyclic motifs mentioned in the review can serve as important resources for the development of COVID-19 treatment methods.

Background: The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro. Methods: Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method. Results: The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC50 value of compound 20 on HeLa cells was 3.9 μM. Conclusion: After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.

Background: Understanding the cognitive and behavioral aspects of Alzheimer's disease- related dementia is surely a sturdy task to deal with. In recent years, a broad search for novel anti-Alzheimer agents has been continuously conducted. The malfunctioning of various neurotransmitter systems and the accumulation of abnormal proteins in the brain are the two key characteristics of this disorder. This is supported by a growing amount of evidence. Some Pharmacophoric groups/combinations exhibit potential neuroprotective activity. Methods: This study aims to compile the most recent and interesting target/target combinations/ pharmacophoric combinations to cure Alzheimer's disease. We concentrated our efforts to find the ability of certain pharmacophoric elements to interfere with various enzymatic and/or receptor systems or to work as neuroprotective agents. These pharmacophoric elements may be proved to be promising leads for future multi-target anti-Alzheimer drug discovery programs. Result: Anticholinesterase drugs were mentioned as the best treatment thus far. Additionally, impairments in the serotonergic, GABAergic, noradrenergic, dopaminergic, and glutaminergic and a few other pathways have all been linked to memory, speech, behavioral and other alterations in Alzheimer's disease. Conclusion: This includes the study of workable pharmacophoric groups/combinations, receptors/ enzymatic systems and related hypotheses to find the promising therapeutic lead compounds which could work as future anti-Alzheimer drugs. We discuss future work that would improve our understanding of this Disease.

Introduction: Based on bioactive group splicing, classical bioisosterism, and the rule of alkene insertion, forty-eight aurone, and indanone derivatives were designed and synthesized. They were evaluated for inhibitory activity against C. albicans, E. coli, and S. aureus. Among them, thirty compounds exhibited moderate to excellent antibacterial activity. Methods: The maximum circle of inhibition was 18 mm (compounds B15, B16, and E7), and the minimum values of MIC and MBC were respectively 15.625 μM (compounds A5 and D2) and 62.5 μM (compounds A6, A8, and E7). Results: The SAR showed that aurone and indanone derivatives could strongly inhibit the growth of Gram-positive bacteria. The introduction of electron-withdrawing groups or hydroxyl is beneficial to the activity. It was exciting that the 3-phenylallylbenzofuranone and 3-allylindanone skeletons with antimicrobial activity were first reported in this study. Compounds A5 and E7 were selected for molecular docking studies with targets MetRS (PBD: 7WPI) and PBP (PDB: 6C3K) to determine the binding interactions at the active site. Conclusion: On this basis, the physicochemical and pharmacological properties of the compounds were predicted and analyzed. The influence of these properties on antimicrobial activity and their implications for subsequent work were discussed. The ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) predictions showed that most of the compounds had good pharmacokinetic profiles and high safety profiles.

Aims and Background: In contrast to antibiotics, metal complexes can realize more than one mechanism of biocidal action to fight multidrug-resistant bacterial strains (due essentially to the metal ions), involving targets like functional groups in the walls of microbial cells and various enzymes. Among the potential antimicrobials are Bi(III) complexes with diphenols. Objective: The present work aimed at synthesizing and investigating novel Bi(III) complexes with Schiff bases as potential antimicrobial and antioxidant agents. Methods: Bi(III) complexes were characterized by means of elemental analysis, FT-IR, UV-Vis, 1H NMR spectroscopy, XRD, cyclic voltammetry and conductivity measurements as well as biological methods. Results: The complexes are characterized by the formula Bi(L)2Cl and pyramidal geometry of their coordination cores BiO2N2Cl, wherein the Bi(III) cation is coordinated by hydroxyl and azomethine moieties. The ligands coordinate in their monoanionic forms. The complexes are more lipophilic and more bioactive against the bacteria tested than the ligands. Both the ligands and their complexes exhibited the capability for the Fe(III)-Cyt c reduction and displayed comparable reducing rates. All the compounds are characterized by the DPPH and ABTS radical scavenging activity, and they are more active reductants than Trolox in the CUPRAC assay too. The peculiarities of the interaction of the complexes with BSA suggest that Cys-34 of BSA is not a major binding site for these complexes. According to molecular docking studies, the complexes bind to BSA via non-covalent interactions. Conclusion: Bi(III) complexation with Schiff bases plays an important role in their antimicrobial and antioxidant activities as well as in their interaction with BSA.

Background:: Textile materials are susceptible to microbial attack as they provide suitable conditions for their growth. The microbes grow with normal body secretions on garments. These microbes are responsible for the weakening, brittleness, and discoloration of the substrate. Furthermore, they cause many health issues to the wearer, including dermal infection, bad odour etc. They threaten the human health as well as create tenderness in fabric. background: Background: Textile materials are susceptible to microbial attack as they provide suitable conditions for their growth. The microbes grow with normal body secretions on garments. These microbes are responsible for the weakening, brittleness, and discoloration of the substrate. Furthermore, they cause many health issues to the wearer including dermal infection, bad odour etc. They threaten the human health as well as create tenderness in fabric. Objectives:: Usually, antimicrobial textiles are prepared by applying antimicrobial finishes after dyeing, which is an expensive approach. Concerning these adversities, in the present study, a series of antimicrobial acid-azo dyes have been synthesized by incorporating antimicrobial sulphonamide moiety into the dye molecules during its synthesis. objective: Objectives: Usually, antimicrobial textiles are prepared by applying antimicrobial finishes after dyeing, which is an expensive approach. Concerning these adversities, in the present study a series of antimicrobial acid-azo dyes has been synthesized by incorporating antimicrobial sulphonamide moiety into the dye molecules during its synthesis. Methods:: A commercially available sulphonamide-based compound, sulfadimidine Na-salt was used as a diazonium component and coupled with different aromatic amines to get desired dye molecules. Since dyeing and finishing are two separate energy-intensive processes, in the current research work, an approach to combine both processes in one step has been adopted that would be economical, time-saving, and environment friendly. Structures of the resultant dye molecules have been confirmed using different spectral techniques such as Mass spectrometry, 1H-NMR spectroscopy, FT-IR, and UV-Visible spectroscopy. method: Methods: A commercially available sulphonamide based compound, sulfadimidine Na-salt was used as diazonium component and coupled with different aromatic amines to get desired dye molecules. Since dyeing and finishing are two separate energy intensive processes, in the current research work an approach to combine both processes in one step have been adopted that would be economical, time saving, and environment friendly. Structures of the resultant dye molecules have been confirmed using different spectral techniques such as Mass spectrometry, 1H-NMR spectroscopy, FT-IR, and UV-Visible spectroscopy. Thermal stability of the synthesized dyes was also determined. These dyes have been applied on wool, and nylon-6 fabrics. Their various fastness properties were examined using ISO standard methods. Results:: Thermal stability of the synthesized dyes was also determined. These dyes have been applied to wool and nylon-6 fabrics. Their various fastness properties were examined using ISO standard methods. Conclusion:: All the compounds exhibited good to excellent fastness properties. The synthesized dyes and the dyed fabrics were screened biologically against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 10536, resulting in significant antibacterial activities. conclusion: n/a other: n/a