Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties

Gogisetti, Gopalarao; Allaka, Tejeswara Rao; Kanna, Umamaheswararao; Basireddy, Sravanthi; Ganta, Ravi Kumar; Sharma, Vishal; Tadiboina, Bhaskara Rao

doi:10.1134/s1068162023030111

Cited by 8 publications

(3 citation statements)

References 59 publications

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“…As a general rule, if the best‐docked conformation of a ligand resembles the bound native ligand in the experimental crystal structure, the used scoring function is said to be successful. According to the method of validation cited in the literature, the successful scoring function is the one in which the RMSD of the best docked conformation is≤2.0 Å from the experimental one [51] . When Figure 5, and 6 is examined, Ligplot poses, 2‐ and 3‐dimensional interactions of compounds 4b , 4d , and 4h in the S. aureus active site are seen.…”

Section: Resultsmentioning

confidence: 99%

“…According to the method of validation cited in the literature, the successful scoring function is the one in which the RMSD of the best docked conformation is � 2.0 Å from the experimental one. [51] When Figure 5, and 6 is examined, Ligplot poses, 2-and 3-dimensional interactions of compounds 4b, 4d, and 4h in the S. aureus active site are seen. Moreover, compound 4b was found to interact favorably with 3FRE protein with a considerable docking score of À 8.13 Kcal/ mol and dissociation constant 4.78 μM.…”

Section: Docking Pose Interactionsmentioning

confidence: 99%

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Synthesis and in Silico Studies of Some New 1,2,3‐Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents

Gujja,

Sadineni,

Epuru

et al. 2023

Chemistry & Biodiversity

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Abstract1,2,3‐Triazole and tetrazole derivatives bearing pyrrolidines are found to exhibit notable biological activity and have become useful scaffolds in medicinal chemistry for application in lead discovery and optimization. Novel indazole bearing 1,2,3‐triazolyltetrazoles were designed as potential antimicrobial candidates. The structure of duel heterocyclics was validated by a spectroscopic technique of infrared (IR), nuclear magnetic resonance (1H and 13C NMR), and mass spectral data. Compounds 4b, 4c, 4d, and 4h were found to have a stronger antibacterial effect against Gram‐positive (S. aureus, B. subtilis, M. Luteus) and Gram‐negative (E. coli, P. aeruginosa) microorganisms with MICs ranging from 5±0.03–18±0.02 μM, respectively. Moreover, scaffolds 4a, 4h showed potent antifungal activity against A. flavus, M. gypsuem strains with MIC values of 10±0.02, 11±0.01 μM, which are similar activity that of the standard Itraconazole (MIC=8±0.02, 10±0.01 μM). The binding mode for compound 4 inside the catalytic pocket of S. aureus complexed with nicotinamide adenine dinucleotide phosphate and trimethoprim and produced a network of hydrophobic and hydrophilic interactions (3FRE). From in silico results, 4b demonstrated highly stable hydrogen binding amino acids Leu62(X) [N18…O, 2.47 Å], Arg44(X) [N17…N, 3.11 Å], Thr96(X) [N10…OG1, 3.05 Å], Gly94(X) [F7…N, 2.82 Å], and Gly43(X) [F7…N, 2.90 Å], which are plays a crucial role in ensuring efficient binding of the ligand in a crystal structure of antibacterial receptor. Furthermore, the physicochemical and ADME filtration molecular properties, estimation of toxicity, and bioactivity scores of these novel scaffolds were evaluated by using SwissADME and ADMETlab2.0 online protocols. Thus, the significant antimicrobial activity of indazole linked to duel heterocyclic compounds can be used for development of new antimicrobial agents with further modifications.

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Section: Resultsmentioning

confidence: 99%

Section: Docking Pose Interactionsmentioning

confidence: 99%

Synthesis and in Silico Studies of Some New 1,2,3‐Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents

Gujja,

Sadineni,

Epuru

et al. 2023

Chemistry & Biodiversity

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“…The basic building block of many medicinal drugs is 1,2,3‐triazole and imidazole, and these analogs have attracted interest in medicinal and pharmaceutical chemistry. Researchers are interested in lead compounds made of 1,2,3‐triazoles with heterocycles because they have a variety of biological properties, including being antibacterial, antifungal, anticonvulsant, antimalarial, antitubercular, anticancer, antiviral, anti‐diabetic, anti‐HIV, anti‐inflammatory, analgesic, and dipole‐dipole bonds with various enzymes, proteins, and receptors [20–27] . 1,2,3‐triazoles as heterocyclic compounds with excellent yield, and this reaction is valuable because azides and acetylacetone are simple to assemble into a single structure is demonstrated by its use in various fields of material and life sciences, such as drug discovery, DNA labeling, and oligonucleotide synthesis (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques

Sadineni,

Reddy Basireddy,

Rao Allaka

et al. 2024

Chemistry & Biodiversity

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A very interesting foundation for this study is the creation of new methods for modifying compounds with a 1,2,3‒triazole and chalcones, as these compounds are significant in organic synthesis as bioactive organic compounds. To contribute to the development of an efficient method for the conversion of antimicrobial and anti‐TB drugs, a novel series of cyclohepta pyridinone fused 1,2,3–triazolyl chalcones were designed and synthesized. All the newly prepared scaffolds were characterized by IR, NMR (1H & 13C) and mass spectrometry. Among the tested compounds, hybrids 8b, 8d, and 8f exhibited exceptional antibacterial susceptibilities with zone of inhibition 27, 32, and 38 mm against the tested E. faecalis bacteria, whereas 8d had better antitubercular potency against M. tuberculosis H37Rv strain with MIC value 5.25 µg/mL. All the synthesized compounds were initially assessed in silico against the targeted protein i.e., DprE1 that indicated compound 8d, 8f and 8h along with several other 1,2,3‐triazole compounds as possible inhibitors. Based on docking results, 8d showed that the amino acids His74(A), Lys76(A), Cys332(A), Asp331(A), Val307(A), Tyr357(A), ect., exhibited highly stable binding to DprE1 receptor of M. tuberculosis (4G3U). Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed.

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Design, Synthesis, in Vitro, and in Silico Evaluations of 1,3,4‐Oxadiazole Derivatives Linked to the Pyrrolo[2,3‐d]pyrimidine Moieties as Potent Antimicrobial Targets

Lal Patel,

Kumar Sureddy,

Boddupalli

et al. 2024

ChemistrySelect

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Abstract1,3,4‐Oxadiazole and its derivatives are well known assorted motif in drug design and development. The development of bacterial infection drug resistance serves as justification for the discovery of novel antimicrobial drugs. Thus, a novel series of 1,3,4‐oxadiazole derivatives linked to pyrrolo[2,3‐d]pyrimidine 6 a–f and 7 a–e was designed, synthesized and fully characterized by 1H‐NMR, 13C‐NMR, FT‐IR and mass spectroscopic analysis. All of the compounds′ in‐vitro antibacterial and antifungal activities were reported, and final oxadiazoles 6 d, 6 e, 6 f, and 7 e showed excellent antimicrobial inhibitory activity as compared to standard drugs. The compounds 6 f and 7 a exhibited potent antifungal activity as a potent inhibitor against C. albicans with MICs 4.0±0.03, 7.5±0.02 μg/mL respectively. In order to determine the different binding interactions that the most active oxadiazoles had with the Staphylococcus aureus DHFR enzyme, a docking study was conducted. The results indicated that the residues of amino acid Thr96(X), Leu62(X), Arg44(X), Asn18(X), Glu17(X), Lys45(X), Thr121(X), Gln95(X), Asp120(X), Ser64(X), Gly94(X), and Phe16(X) had promising energy value, within the range of −6.84 to −9.63 kcal/mol (PDB: 3FRA). The most effective inhibitors, 6 and 7, also underwent in silico ADMET tests to predict their pharmacokinetic and physicochemical characteristics.

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Synthesis, Anticancer Activity and Computational Docking Techniques of Some Novel Derivatives Based on Indole Bearing Oxadiazole–Triazole Moieties

Cited by 8 publications

References 59 publications

Synthesis and in Silico Studies of Some New 1,2,3‐Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents

Synthesis and in Silico Studies of Some New 1,2,3‐Triazolyltetrazole Bearing Indazole Derivatives as Potent Antimicrobial Agents

Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques

Design, Synthesis, in Vitro, and in Silico Evaluations of 1,3,4‐Oxadiazole Derivatives Linked to the Pyrrolo[2,3‐d]pyrimidine Moieties as Potent Antimicrobial Targets

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