Antibacterial Pharmacophore Research Articles

Synthesis, ADME Profiling, Antibacterial Screening and Molecular Docking of Some New Tetrazole‐Heterocycle Hybrids

AbstractOver the past 20 years, there has been a notable rise in the incidence of invasive bacterial infections. This increase has been mostly linked to the growth of drug‐resistant bacteria. Tetrazoles have been considered as promising antibacterial agents and their effectiveness may be enhanced by hybridization with other antibacterial pharmacophores. In this work, a series of tetrazole hybrids (1‐6) containing oxazepane and pyrazole rings as well as Mannich bases (7,8) were synthesized via the Schiff and Mannich reactions, respectively. The compositions were proven spectroscopically using infrared spectra, proton (1H) and carbon‐13 (13C) nuclear magnetic resonance spectra and elemental analyses. Moreover, the pharmacokinetic properties viz Absorption, Distribution, Metabolism and Excretion (ADME) were predicted in silico using SwissADME server. Compounds 1,2 and 4–6 attaining the best drug‐likeness properties were screened for their antibacterial activities against Staphylococcus epidermidis and Streptococcus mutans at different concentrations in comparison with tetracycline and amikacin, respectively. Afterwards, a molecular docking study was performed to explore the potential binding patterns of the new antibacterial compounds. Collectively, the tetrazole hybrids 4 and 5 have been found to have higher inhibitory potencies compared to tetracycline, serving them as potential antibacterial candidates which can be further optimized in the future.

Efficient synthesis, crystallographic study, antimicrobial activity and in silico studies of novel bioactive α-aminophosphonates based on pyridine moiety

This study articulates the synthesis, spectroscopic characterization, antimicrobial evaluation, theoretical calculations, and molecular docking analysis of a novel α-aminophosphonates derived from aminopyridine as potential antibacterial pharmacophore. The structures of all compounds was established using FTIR, 1H, 13C, 31P NMR spectroscopy. A single crystal of the studied compound 3g was selected for X-ray diffraction analysis, it crystallizes in the monoclinic crystal system with P 21/n space group. Theoretical studies based on density functional theory (DFT) at the B3LYP /6-31G (d, p) level of theory was utilized to investigate the stability and electronic properties electronic of the studied α-aminophosphonates. The ADME/toxicity analyzes carried out by Swiss ADME and OSIRIS software show that all synthesized molecules exhibited good pharmacokinetics, bioavailability and had no toxicity profile.

Chloramphenicol Derivatization in Its Primary Hydroxyl Group with Basic Amino Acids Leads to New Pharmacophores with High Antimicrobial Activity.

In a previous study published by our group, successful modification of the antibiotic chloramphenicol (CHL) was reported, which was achieved by replacing the dichloroacetyl tail with alpha and beta amino acids, resulting in promising new antibacterial pharmacophores. In this study, CHL was further modified by linking the basic amino acids lysine, ornithine, and histidine to the primary hydroxyl group of CHL via triazole, carbamate, or amide bonding. Our results showed that while linking the basic amino acids retained antibacterial activity, it was somewhat reduced compared to CHL. However, in vitro testing demonstrated that all derivatives were comparable in activity to CHL and competed for the same ribosomal binding site with radioactive chloramphenicol. The amino acid-CHL tethering modes were evaluated either with carbamate (7, 8) derivatives, which exhibited higher activity, or with amide- (4-6) or triazole-bridged compounds (1-3), which were equally potent. Our findings suggest that these new pharmacophores have potential as antimicrobial agents, though further optimization is needed.

Recent Advances in Quinolone Hybrids With Potential Antibacterial Activity Against drug-resistant Bacteria

Quinolone derivatives, represented by fluoroquinolones, haveemerged as the most commonly prescribed antibacterials for the treatment of various bacterial infections. In particular, the combination of aquinolone moiety with other antibacterial pharmacophores has the potential to act on different drug targets, which in turn, overcome drug resistance. Accordingly, quinolone hybrids are useful prototypes for fightingdrug-resistant pathogens. The purpose of the present reviewis to provide an emphasis on the current scenario of quinolone hybrids with potential antibacterial activity against drug-resistant pathogens, covering articles published in the past 10years. The structure-activity relationships, various aspects of rational designand mechanisms of action are also discussed to facilitate further rational development of more effective candidates.

Thiazole-pyrazoline hybrids as potential antimicrobial agent: Synthesis, biological evaluation, molecular docking, DFT studies and POM analysis

In this study, an efficient synthesis of new thiazole-pyrazoline hybrids was investigated and hybrids were screened for their antimicrobial activities against four species of pathogenic bacteria and one fungal strain utilizing the well-diffusion and MIC assays using ciprofloxacin and fluconazole as the positive controls. The obtained results revealed excellent to moderate antibacterial and antifungal activity. Among them, compound 11b showed potent antibacterial activity against A. baumannii with MIC of 16 µg/mL, while ciprofloxacin was ineffective. Molecular docking studies showed that compound 11b had a stronger binding affinity of about 1 kcal/mol to gram-positive and gram-negative bacteria than compared with compound 11a. Furthermore, the results of the POM (Petra, Osiris, Molinspiration) bioinformatics investigations show that the two studied heterocycles present a very good non toxicity profile, a bad bioavailability, and pharmacokinetics. Finally, an antibacterial pharmacophore (Nδ−, HNδ−) and two antifungal pharmacophores (Nδ−, Sδ−) and (Nδ−, Nδ−) were evaluated in the POM investigations and deserves all our attention to be tested against other pathogenic microorganisms. The more potent compound 11b compared to that of 11a can also be attributed to its lower HOMO-LUMO gap which is an indicator of greater reactivity.

Glenthmycins A-M: Macrocyclic Spirotetronate Polyketide Antibacterials from the Australian Pasture Plant-Derived Streptomyces sp. CMB-PB041.

Chemical investigation of Australian pasture plant-derived Streptomyces sp. CMB-PB041, supported by miniaturized cultivation profiling and molecular network analysis, led to the isolation and characterization of 13 new macrocyclic spirotetronates, glenthmycins A-M (1-13), with structures assigned by detailed spectroscopic analysis, chemical degradation and derivatization, and mechanistic and biosynthetic considerations. Hydrolysis of glenthmycin B (2) yielded the aglycone 14, whose structure and absolute configuration were secured by X-ray analysis, along with the unexpected amino sugar residues glenthose lactams A (15) and B (16), with Mosher analysis of 15 facilitating assignment of absolute configurations of the amino sugar. While the glenthmycins proved to be acid stable, treatment of isomeric glenthmycins (i.e., 3, 6, and 8) with base catalyzed rapid intramolecular trans-esterification to regio-isomeric mixtures (i.e., 3 + 6 + 8). Exposure of 5 to base achieved the same intramolecular trans-esterification and was instrumental in detecting and tentatively identifying two additional minor co-metabolites, glenthmycins N (19) and O (20). A structure-activity relationship analysis carried out on 1-13 and the semisynthetic analogues 14 and 21-26 revealed a promising Gram +ve antibacterial pharmacophore, effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), but with no detectable cytotoxicity to eukaryotic cells (i.e., fungal and human carcinoma). Of particular note, the semisynthetic analogue glenthmycin K 9-valerate (26) was unique among glenthmycins in potently inhibiting growth of the full panel of Gram +ve pathogens (IC50 0.2-1.6 μM). We conclude with an observation that any future evaluation of the antibacterial potential of glenthmycins and related macrocyclic spirotetronates may do well to include important soil-derived Gram +ve pathogens, such as Bacillus anthrax, Clostridium botulinum, and Rhodococcus equi, the causative agents of anthrax, botulism, and livestock pneumonia.

The Antibacterial Activity of Isatin Hybrids.

Bacterial infections, which cause a wide range of host immune disorders leading to local and systemic tissue damage, are still one of the main causes of patient morbidity and mortality worldwide. Treatment of bacterial infections is challenging, mainly attributed to the rapidly evolving resistance mechanisms, creating an urgent demand to develop novel antibacterial agents. Hybridization is one of the most promising strategies in the development of novel antibacterial drugs with the potential to address drug resistance since different pharmacophores in the hybrid molecules could modulate multiple targets and exert synergistic effects. Isatin, distributed widely in nature, can exert antibacterial properties by acting on diverse enzymes, proteins, and receptors. Accordingly, hybridization of isatin pharmacophores with other antibacterial pharmacophores in one molecule may provide novel antibacterial candidates with broad-spectrum activity against various pathogens, including drug-resistant forms. This review aims to outline the recent advances of natural and synthetic isatin hybrids with antibacterial potential and summarizes the structure-activity relationship (SAR) to provide an insight for the rational design of more active candidates, covering articles published between January 2012 and June 2021.

Oxazolidinone-containing Hybrids with Antibacterial Activity against Methicillin-resistant Staphylococcus aureus (MRSA): A Mini-review.

The increasing danger of methicillin-resistant Staphylococcus aureus (MRSA) and the limited therapeutic options for invasive MRSA infections make an urgent demand for the development of novel anti-MRSA agents. Oxazolidinone derivatives could inhibit protein synthesis by acting on the ribosomal 50S subunit of the bacteria and prevent the formation of a functional 70S initiation complex, so oxazolidinones are a novel class of antimicrobial agents with potential activity against a wide range of clinically significant multidrug-resistant Gram-positive pathogens. However, oxazolidinones such as linezolid are associated with significant adverse events, and myelosuppression represents the main unfavorable side effects. Moreover, MRSA isolates that are resistant to oxazolidinones have already emerged. Hybridization of oxazolidinone with other antibacterial pharmacophores has the potential to interact with multiple targets or to counterbalance the known side effects associated with each pharmacophore. Thus, oxazolidinone-containing hybrids are useful scaffolds for the development of novel anti-MRSA agents. This review covers the recent advances of oxazolidinonecontaining hybrids with anti-MRSA activity developed in the last decade to set up the direction for the design and development of oxazolidinone-containing hybrids with high efficiency and low toxicity.

Synthesis and antimicrobial activity evaluation of some new 7-substituted quinolin-8-ol derivatives: POM analyses, docking, and identification of antibacterial pharmacophore sites

Abstract Eight new 7-substituted quinolin-8-ol derivatives were synthesized moderate to good yields through quinolin-8-ol, and secondary amines as the starting reagents. The structures of the prepared compounds have been characterized by elemental analysis and 1H/13C NMR. The antimicrobial activity of this new series of heterocyclic compounds has been achieved in vitro against some bacterial strains by means of the disk method, and most of the tested compounds have shown comparable or greater antibacterial activity than nitroxoline (standard antibiotic). It was very motivating to observe that POM (Petra/Osiris/Molinspiration) bioinformatic analyses of compound 5 exhibited better antibacterial activity (MIC = 10 μg/mL against B. subtilis bacteria), and higher drug score (DS = 0.57) compared with Nitroxoline (DS = 0.47; MIC = 20 μg/mL). Molecular docking investigations were also conducted to investigate the binding affinities as well as interactions of some compounds with the target proteins.

Coumarin-containing hybrids and their antibacterial activities.

Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Several coumarin-containing hybrids such as coumermycin A1, clorobiocin, and novobiocin have already been used in clinical practice for the treatment of various bacterial infections; thus, it is conceivable that hybridization of the coumarin moiety with other antibacterial pharmacophores may provide opportunities for the development of novel antibiotics. This review outlines the advances in coumarin-containing hybrids with antibacterial potential in the recent 5 years and the structure-activity relationships are also discussed.

Antibiotics in the clinical pipeline in October 2019.

The development of new and effective antibacterial drugs to treat multi-drug resistant (MDR) bacteria, especially Gram-negative (G−ve) pathogens, is acknowledged as one of the world’s most pressing health issues; however, the discovery and development of new, nontoxic antibacterials is not a straightforward scientific task, which is compounded by a challenging economic model. This review lists the antibacterials, β-lactamase/β-lactam inhibitor (BLI) combinations, and monoclonal antibodies (mAbs) first launched around the world since 2009 and details the seven new antibiotics and two new β-lactam/BLI combinations launched since 2016. The development status, mode of action, spectra of activity, lead source, and administration route for the 44 small molecule antibacterials, eight β-lactamase/BLI combinations, and one antibody drug conjugate (ADC) being evaluated in worldwide clinical trials at the end of October 2019 are described. Compounds discontinued from clinical development since 2016 and new antibacterial pharmacophores are also reviewed. There has been an increase in the number of early stage clinical candidates, which has been fueled by antibiotic-focused funding agencies; however, there is still a significant gap in the pipeline for the development of new antibacterials with activity against β-metallolactamases, orally administered with broad spectrum G−ve activity, and new treatments for MDR Acinetobacter and gonorrhea.

Synthesis, characterization, X-Ray crystal study and bioctivities of pyrazole derivatives: Identification of antitumor, antifungal and antibacterial pharmacophore sites

The reaction of hydroxymethyl pyrazole derivatives with one equivalent of the appropriate primary amine yields N-((1h-pyrazol-1-yl) methyl) pyrimidin-2-amine (L1), 2-(((1h-pyrazol-1-yl) methyl) amino) benzoic acid (L2), and ethyl 5-methyl-1-(((6-methyl-3-nitropyridin-2-yl) amino) methyl)-1h-pyrazole-3-carboxylate (L3). The structure of synthesized compounds (L1-L3) was identified by FT-IR, UV–visible, proton NMR spectroscopy, mass spectroscopy, and single crystal X-ray crystallography. The armed pyrazoles (L1-L3) were crystallized in the space groups C2/c, P21/n and P-1 for L1, L2, and L3 respectively. Crystallographic analysis revealed that N–H of the amine group and Nitrogen or Oxygen atoms are in-plane with the aromatic ring. The aminomethyl chain forms a distorted second plane. The angle between the two planes is observed to be 76.07° (N2–C7–N5–N19) for L1, 62.12° (N34–C63–N22–N35) for L2, 60.84° (N3–C8–N2–N1), and 0.41° (N1–C4–C3–O1/O2) for L3 was studied. Theoretical physical and chemical properties calculations have been performed on the studied armed pyrazoles (L1-L3) using three different programs: Petra, Osiris, & Molinspiration (POM). The geometric parameters of the optimized structure are in agreement with the experimental data obtained from the X-ray structures. The origin of the biological activity against breast cancer and microbes has also been confirmed.

Antibacterial and antioxidant aryl-enclosed macrocyclic polyketide from intertidal macroalgae associated heterotrophic bacterium Shewanella algae

Previously unreported aryl-enclosed 12-membered macrocyclic polyketide characterised as 2′-[(8-ethyl-8-methyl-2,5-dioxo-1-oxacyclododecanyl)methoxy]-methyl benzoate, was identified from the organic extract of Shewanella algae, a heterotrophic gamma proteobacterium, isolated from an intertidal marine macroalgae Hypnea valentiae. The titled macrocyclic polyketide displayed potential antibacterial activity (minimum inhibitory concentration 3.75 µg/mL) compared to that exhibited by chloramphenicol (6.25 µg/mL). Potent antioxidant activity of the studied compound was characterised by its greater scavenging effects on 2,2-diphenyl-1-picrylhydrazyl radical and 2,2′-azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (IC50 0.59 and 0.53 mg/mL, respectively) compared with standard, α-tocopherol (IC50 > 0.65 mg/mL). In silico molecular docking studies of the polyketide with the penicillin binding protein active sites encoded in methicillin resistant Staphylococcus aureus core genome displayed lesser binding energy of −10.31 kcal/mol, which could be correlated with its in vitro antibacterial activities. Structure-activity correlation studies demonstrated the direct relationship of electronic and optimum hydrophobic properties of the macrocyclic polyketide with its bioactivities. Therefore, the presently studied aryl-enclosed macrocyclic compound could be utilised as potent antioxidant and antibacterial pharmacophore in the medicinal formulations.

Current scenario of tetrazole hybrids for antibacterial activity

The incidence of invasive bacterial infections has increased remarkably over the past two decades, which was mainly attributed to the increasing emergence of drug-resistant bacteria especially multidrug-resistant strains, intractable pathogens and newly arising pathogenic organisms. Tetrazoles, the bioisoster of carboxylic acid, possess considerable antibacterial property. Hybridization of tetrazole with other antibacterial pharmacophores has the potential to enhance the efficacy against both drug-sensitive and drug-resistant pathogens. Some tetrazole hybrids such as tetrazole-oxazolidinone hybrid Tedizolid 25 and Tedizolid phosphate 26 have already been marketed for the treatment of acute bacterial skin and skin structure infections caused by various bacteria. DA-7867 (27), the amide analog of Tedizolid, also exhibited promising activities against a panel of clinically important pathogens including drug-resistant organisms, demonstrating the possible utility of the tetrazole scaffolds in the development of new antibacterial agents. Thus, hybridization of tetrazole with other antibacterial pharmacophores represents a promising strategy to develop novel antibacterial candidates. This work is attempted to systematically review the research of tetrazole hybrids in the design and development of antibacterial agents during the past two decades. The structure-activity relationship (SAR) is also discussed to provide an insight for rational design of more effective tetrazole antibacterial candidates.

Antibacterial activity study of 1,2,4-triazole derivatives

Antibiotics are commonly used to fight against bacterial infections, but bacteria have already been resistant to almost all antibiotics due to abuse of antibiotics. 1,2,4-Triazole derived compounds possess chemotherapeutic effects including potential antibacterial activities against drug-sensitive as well as drug-resistant pathogens. Hybridization displays a high potential to develop novel drugs with the capacity to overcome drug resistance, reduce toxicity and improve pharmacokinetic profiles. More effective antibacterial candidates might be obtained by the hybridization of 1,2,4-triazole with other antibacterial pharmacophores. This review summarizes the recent advances of 1,2,4-triazole derivatives as potential antibacterial compounds, and the structure-activity relationship is also discussed.

Very Short and Stable Lactoferricin-Derived Antimicrobial Peptides: Design Principles and Potential Uses.

The alarming rate at which micro-organisms are developing resistance to conventional antibiotics represents one of the global challenges of our time. There is currently ample space in the antibacterial drug pipeline, and scientists are trying to find innovative and novel strategies to target the microbial enemies. Nature has remained a source of inspiration for most of the antibiotics developed and used, and the immune molecules produced by the innate defense systems, as a first line of defense, have been heralded as the next source of antibiotics. Most living organisms produce an arsenal of antimicrobial peptides (AMPs) to rapidly fend off intruding pathogens, and several different attempts have been made to transform this versatile group of compounds into the next generation of antibiotics. However, faced with the many hurdles of using peptides as drugs, the success of these defense molecules as therapeutics remains to be realized. AMPs derived from the proteolytic degradation of the innate defense protein lactoferrin have been shown to display several favorable antimicrobial properties. In an attempt to investigate the biological and pharmacological properties of these much shorter AMPs, the sequence dependence was investigated, and it was shown, through a series of truncation experiments, that these AMPs in fact can be prepared as tripeptides, with improved antimicrobial activity, via the incorporation of unnatural hydrophobic residues and terminal cappings. In this Account, we describe how this class of promising cationic tripeptides has been developed to specifically address the main challenges limiting the general use of AMPs. This has been made possible through the identification of the antibacterial pharmacophore and via the incorporation of a range of unnatural hydrophobic and cationic amino acids. Incorporation of these residues at selected positions has allowed us to extensively establish how these compounds interact with the major proteolytic enzymes trypsin and chymotrypsin and also the two major drug-binding plasma proteins serum albumin and α-1 glycoprotein. Several of the challenges associated with using AMPs relate to their size, susceptibility to rapid proteolytic degradation, and poor oral bioavailability. Our studies have addressed these issues in detail, and the results have allowed us to effectively design and prepare active and metabolically stable AMPs that have been evaluated in a range of functional settings. The optimized short AMPs display inhibitory activities against a plethora of micro-organisms at low micromolar concentrations, and they have been shown to target resistant strains of both bacteria and fungi alike with a very rapid mode of action. Our Account further describes how these compounds behave in in vivo experiments and highlights both the challenges and possibilities of the intriguing compounds. In several areas, they have been shown to exhibit comparable or superior activity to established antibacterial, antifungal, and antifouling commercial products. This illustrates their ability to effectively target and eradicate various microbes in a variety of settings ranging from the ocean to the clinic.

Chlorinated emodin as a natural antibacterial agent against drug-resistant bacteria through dual influence on bacterial cell membranes and DNA

The rise in infections caused by drug-resistant pathogens and a lack of effective medicines requires the discovery of new antibacterial agents. Naturally chlorinated emodin 1,3,8-trihydroxy-4-chloro-6-methyl-anthraquinone (CE) from fungi and lichens was found to markedly inhibit the growth of Gram-positive bacteria, especially common drug-resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). CE was confirmed to cause significant potassium leakage, cell membrane depolarization and damage to the selective permeability of cell membranes in bacterial cells, resulting in bacterial cell death. In addition, CE was shown to have a strong electrostatic interaction with bacterial DNA and induce DNA condensation. Thus, CE is a promising natural antibacterial pharmacophore against Gram-positive bacteria, especially common drug-resistant MRSA and VRE isolates, with a dual antibacterial mechanism that damages bacterial cell membranes and DNA.

Antibiotics in the clinical pipeline at the end of 2015.

There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health. Action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics. This review lists the 30 antibiotics and two β-lactamase/β-lactam combinations first launched since 2000, and analyzes in depth seven new antibiotics and two new β-lactam/β-lactamase inhibitor combinations launched since 2013. The development status, mode of action, spectra of activity and genesis (natural product, natural product-derived, synthetic or protein/mammalian peptide) of the 37 compounds and six β-lactamase/β-lactam combinations being evaluated in clinical trials between 2013 and 2015 are discussed. Compounds discontinued from clinical development since 2013 and new antibacterial pharmacophores are also reviewed.

Structure and POM analyses of 2-{(2Z)-2-[(2R)-2-ethoxy-4-oxo-2H-chromen-3(4H)-ylidene]hydrazinyl}benzonitrile with promising parasitological activity

Functionalised chromanone (4) is prepared by the condensation of aryldiazonium salt (2) and enaminones (1) in ethanol at room temperature. The structure of (4) was determined by spectral (IR, 1H and 13C NMR), elemental and X-ray diffraction analysis. Compound 4 (C18H15N3O3) crystallizes in the monoclinic space group P21/c with a = 7.9182(5), b = 21.729(2), c = 9.6217(7) A, β = 97.293(6)°, V = 1642.0(2) A3, Z = 4. The molecule of compound (4) is bent at the C-16 atom with a C15–O2–C16–C8 torsion angle of 46.18(3)°. Intramolecular phenolic N–H···O hydrogen bonds are also formed. Intermolecular hydrogen bonding and π–π stacking hold the molecules together. The average distance between stacked benzene ring planes is 4.488(12) A. The preliminary POM analyses of 4 confirm the coexistence of two combined antibacterial and antiparasite pharmacophore sites. Therefore, compound 4 is promising and it should be screened without hesitation against virulent and pathogenic biotargets.

Synthesis, spectral characterization of some new 3-heteroaryl azo 4-hydroxy coumarin derivatives and their antimicrobial evaluation

In the present research study, 3-heteroarylazo 4-hydroxy coumarin derivatives were synthesized and evaluated in vitro for their preliminary antibacterial activities against four different pathogenic bacterial strains such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. Antibacterial activity of each compound was compared with standard drug, Ampicillin. The compounds were interpreted by UV, IR, 1H NMR, mass spectroscopy and X-ray diffraction studies. Solvatochromic behaviour of these compounds was also investigated by UV–vis spectra. Zone of inhibition and minimum inhibitory concentration revealed that all the products exhibited greater antibacterial potential against all bacterial strains except 4g.3-Thiazolylazo and 3-(4-phenyl thiazolylazo) of 4-hydroxy coumarin, which have been exhibiting good zone of inhibition against both gram +ve strains and gram −ve strains, where as the compound pyrazolone azo analogue 4e has tremendous antibacterial activity. Finally we concluded that the compounds having thiazole, pyrazole and triazole nucleus in individual molecular structure clubbed with potent antibacterial pharmacophore of 4-hydroxy coumain showed antibacterial activities.