Design, Synthesis and Pharmacological Evaluation of New Thiazole Derivatives as Anthelmintic Agents

2020 ◽  
Vol 13 (5) ◽  
pp. 5075-5081
Author(s):  
Sirisha Kalam ◽  
Sai Krishn G ◽  
Kumara Swamy D ◽  
Sai Santhoshi K ◽  
Durga Prasad K
Keyword(s):  
Anthelmintic Activity ◽  
Docking Studies ◽  
Molecular Property ◽  
Thiazole Derivatives ◽  
Pharmacological Agents ◽  
Design Synthesis ◽  
Standard Drug ◽  
Lipinski’S Rule ◽  
Mass Spectral ◽  
Tubulin Protein

Pharmacological agents that kills parasites are essential drugs in some tropical countries. In this study, a series of 2-amino substituted 4-phenyl thiazole derivatives (4a-e) have been synthesized by the conventional method. The thiazole derivatives were synthesized by three steps. The obtained five derivatives were purified by recrystallization using methanol as a solvent or column chromatography. They were characterized by melting point, TLC, FTIR, 1H NMR and MASS spectral data. Compounds 4a-e were evaluated in silico by using different software’s (Lipinski’s Rule of 5, OSIRIS molecular property explorer, Molsoft molecular property explorer, and PASS & docking studies). These compounds were then evaluated for their possible anthelmintic activity against Indian adult earth worms (Pherituma postuma). All the compounds displayed significant anthelmintic activity. Compound 4c and 4e were more potent compounds when compared with the standard drug (mebendazole). Molecular docking studies guided and proved the biological activity against beta tubulin protein (1OJ0). In conclusions, these new molecules have promising potential as anthelmintic for treatment of parasites.   

scholarly journals Design, Synthesis and Molecular Modeling Studies of Thiosemicarbazone & Thiazole Derivatives as Potential Anti-Malarial Agents

2021 ◽  
Author(s):  
Kamalpreet Kaur ◽  
Vivek Asati
Keyword(s):  
Antimalarial Activity ◽  
Docking Study ◽  
Docking Studies ◽  
Amino Acid Residues ◽  
Thiazole Derivatives ◽  
Design Synthesis ◽  
Standard Drug ◽  
Reference Drug ◽  
Electron Withdrawing Group ◽  
Drug Compound

Abstract A series of novel thiosemicarbazone & thiazole derivatives (Kp1-10) have been designed, synthesized and evaluated for potential anti-malarial activity. The antimalarial activity of the synthesized thiazole derivatives (Kp1-10) was assessed against human pathogenic malarial strain viz. Plasmodium falciparum while quinine was taken as the standard drug. compound Kp-9 was found to be most promising which exhibited strongest inhibitory activity against P. falciparumwith an IC50 value of 0.29µg/mL which was higher than the reference drug quinine (1.26µg/mL). The SAR studyrevealed that thesubstitution with electron withdrawing group at phenyl increases anti-malarial activity as shown in compound Kp-9. The result of molecular docking studies showed that compounds Kp-9, Kp-1, Kp-3, Kp-4 showed good docking scores with protein (PDB code: 5TBO). The compound Kp-9 showed highest docking score (-9.519). Whereas, compounds Kp-1, Kp-3, Kp-4 and Kp-10 showed good docking scores (-8.764, -8.406, -9.062, -9.435 respectively) with critical interactions with the amino acid residues such as VAL532, ILE237, LEU531, HIE185, TYR528, ASN274, ARG265. The results of biological activity and docking study revealed that the presence of electron withdrawing group at 4th position of phenyl ring attached is crucial for better anti-malarial activity and favorable drug-like profile which can emerge as a potential drug molecule in further development.

scholarly journals INSILICO DESIGN, SYNTHESIS AND CHARACTERIZATION OF SOME NOVEL BENZOTHIAZOLE DERIVATIVES AS ANTI-CANCER AGENTS

2017 ◽  
Vol 10 (4) ◽  
pp. 150
Author(s):  
Leena K Pappachen ◽  
Subin Mary Zachariah ◽  
Deepthy Chandran
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Mass Spectral ◽  
Benzothiazole Derivatives ◽  
Anti Cancer ◽  
Mcf 7

Objectives: Cancer is a disease characterized by uncontrollable, irreversible, independent, autonomous, uncoordinated and relatively unlimited and abnormal over growth of tissues. Breast cancer is the second most common type of cancer after lung cancer. The aim of the study is to carry out the docking studies, synthesis and anti-tumour activities  of Benzothiazole derivatives containing oxadiazole groups or amino groups.Methods: The docking studies of benzothiazole derivatives were done with known anti-cancer targets like oestrogen receptor by using argus lab and auto dock programmes with the standard drug tamoxifen. Based upon  the results obtained from the molecular modeling, the derivatives were selected for the synthesis. The synthesized compounds were characterized by melting point, TLC, IR, 1H NMR, 13CNMR, MASS spectral data and screened for their in- vitro anti-cancer activities.Results: The docking scores obtained for benzothiazole derivatives (BT1,BT2,BT3,BT4) and std.tamoxifen  from the preliminary docking program by using  argusLab  were- 9.68,-9.4,-9.59, -11.1988,-9.71 and  by using autodock program were -6.29, -5.25,-7.19,-7.48,-3.86 respectively. All the four derivatives were synthesized, characterized and subjected to in vitro anticancer screening by MTT assay in breast cancer (MCF-7) cell lines. Compounds DBT1, DBT2, DBT3 were the most active compounds against MCF-7 cell lines with IC50 of 70.0, 64.0 and 65.0, respectively.Conclusion: All the four  derivatives show  good docking scores when compared to standard drug and can be concluded that all the synthesized benzothiazole  ligands show good anti-cancer property.Keywords: Benzothiazole, Oxadiazole, Estrogen receptor, Anticancer targets.

scholarly journals Design, Synthesis and Antimicrobial Evaluation of Novel 2-Thiobenzimidazole Derivatives: in silico and in vitro Approach

2020 ◽  
Vol 32 (11) ◽  
pp. 2753-2762
Author(s):  
C. Naresh Babu ◽  
S. Triveni ◽  
M. Vijaya Jyothi ◽  
B. Yamuna ◽  
A. Yamini
Keyword(s):  
Antimicrobial Agents ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Molecular Structures ◽  
Benzimidazole Derivatives ◽  
Design Synthesis ◽  
Lipinski’S Rule ◽  
Mass Spectral ◽  
Subunit B

The development of potent antimicrobial agents is more essential due to resistance developed in microorganisms towards the existing drugs. The diversity in the biological retort profile of benzimidazole more attracted the attention to develop novel compounds to its various potential against microorganisms. In present work, designed molecular structures docked against DNA gyrase subunit B and lanosterol 14α-demethylase (LAD) proteins. Interestingly, most of the compounds revealed excellent docking scores and interactions compared with the co-crystal ligands KKK, 1YN of LAD proteins 3LD6, 5V5Z than DNA gyrase subunit B proteins 5L3J and 4P8O. Then, the molecular properties were predicted by the Swiss ADME tool, the compounds showed no violation in Lipinski’s rule and good synthetic accessibility. These compounds synthesized by stirring of 2-mercapto benzimidazole (1), epichlorohydrin (2) in the presence of sodium hydroxide gives 1-(1H-benzo[d]imidazole-2-ylthio)-3- chloropropan-2-ol (3), which upon refluxing with different substituted aliphatic and aromatic amines in methanol produces novel benzimidazole derivatives (4a-l). These compounds were characterized by their melting point, FT-IR, 1H NMR and Mass spectral data. The synthesized molecules screened for antibacterial and antifungal activity. The compound 4l exhibited excellent activity at MIC 0.4 μg/mL against C. albicans. Compounds 4c and 4e showed MIC at 3.12 μg/mL against E. coli and the compounds 4l and 4J exhibited MIC at 3.12 μg/mL against S. aureus. Docking studies and activity result reveals the novel benzimidazole compound 4l has excellent antifungal and antibacterial effect.

scholarly journals SYNTHESIS, CHARACTERIZATION, AND ANTHELMINTIC ACTIVITY OF NOVEL BENZOTHIAZOLE DERIVATIVES CONTAINING INDOLE MOIETIES

2019 ◽  
pp. 321-325
Author(s):  
ALETI RAJAREDDY ◽  
SRINIVAS MURTHY M
Keyword(s):  
Spectral Analysis ◽  
Fourier Transform ◽  
Infrared Spectroscopy ◽  
Magnetic Resonance ◽  
Fourier Transform Infrared Spectroscopy ◽  
Anthelmintic Activity ◽  
Mass Spectral Analysis ◽  
Standard Drug ◽  
Mass Spectral ◽  
Benzothiazole Derivatives

Objective: The objective of this study was to synthesize and evaluate the anthelmintic activity (AA) of novel benzothiazole derivatives containing indole moieties (BDIM). Methods: The present works which involve the substituted isatin Schiff bases undergo acetylating and reacting with 2-aminobenzothiazole to give novel BDIM. Results: All the newly synthesized molecules (5a-5o) were characterized by Fourier-transform infrared spectroscopy, H_nuclear magnetic resonance, and mass spectral analysis along with physical data. The biological potentials of the newly synthesized compounds are evaluated for their AA using an Indian earthworm (Pheretima posthuma), and albendazole was used as standard drug. Conclusion: The synthesized compound 5f, 5n, and 5o showed good AA, whereas others exhibited significant activities.

scholarly journals MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

2017 ◽  
Vol 10 (9) ◽  
pp. 392 ◽  
Author(s):  
Peter Juma Ochieng ◽  
Tony Sumaryada ◽  
Daniel Okun
Keyword(s):  
Molecular Docking ◽  
Surface Area ◽  
Docking Studies ◽  
Polar Surface Area ◽  
Autodock Vina ◽  
Standard Drug ◽  
Lipinski’S Rule ◽  
Structure Activity ◽  
Topological Polar Surface Area ◽  
High Binding Affinity

  Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski’s rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Novel Imidazopyridine Analogues as Proton Pump Antagonist

2020 ◽  
Vol 32 (4) ◽  
pp. 776-782
Author(s):  
Ravindra S. Sonawane ◽  
Kiran D. Patil ◽  
Avinash V. Patil
Keyword(s):  
Spectral Analysis ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Docking Studies ◽  
Design Synthesis ◽  
Standard Drug ◽  
Imidazopyridine Derivatives

A series of novel imidazopyridine derivatives as proton pump inhibitors was designed with compounds of CID data base and explored considering AZD0865 as standard. Many compounds were identified and docked in proton pump ATPase pocket (PDB ID: 4ux2). Molecular docking studies revealed that many compounds showed good proton pump ATPase inhibitory activity. The docking poses revealed the interaction of ligands with amino acid. The standard drug AZD0865 had docking score of -7.112302 and displayed interactions with Asn138 and Asp137. A series of novel imidazopyridine derivatives as proton pump inhibitors were docked, synthesized and characterized by IR, NMR, CHN and MS spectral analysis. The target imidazopyridines were prepared from substituted 2-aminonicotinic acid and 2-bromo-1-substituted ethanone. in vitro Studies explained that few compounds exhibited moderate to good proton pump ATPase inhibitory activity in comparison with the reference drugs i.e. AZD0865. Compounds 11 and 12 shown higher activities with the IC50 4.3. Compounds 1, 4, 6, 7, 8, 10 and 13 showed weak anti-ulcer activity with its IC50 5.2, 5.8, 5.5, 5.1, 4.9, 4.6 and 5.9 and positive control AZD0865 shown IC50 2.0.

scholarly journals Synthesis and Molecular Docking Studies of Triazole Conjugated Novel 2,4-Disubstituted Thiazole Derivatives as CDK2 Inhibitors

2021 ◽  
Vol 33 (8) ◽  
pp. 1849-1854
Author(s):  
M. Narasimha ◽  
B. Revanth ◽  
D. Mahender ◽  
P. Sarita Rajender
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Oral Absorption ◽  
Binding Capacity ◽  
Docking Studies ◽  
Thiazole Derivatives ◽  
Molecular Docking Studies ◽  
Mass Spectral ◽  
Drug Molecules ◽  
New Chemical Entities

A series of triazole conjugated novel 2,4-disubstituted thiazole derivatives (9a-l) were synthesized from salicylaldehyde. These new chemical entities were characterized by their IR, 1H & 13C NMR, mass spectral data and their molecular docking studies were performed to identify potential inhibitors of CDK2 protein. The synthesized analogs 9a-l were docked with CDK2 protein (PDB: 1GIJ). Among these 9h, 9j and 9k showed better Glide score, Prime MM-GBSA and ADME properties as compared to seliciclib and dinaciclib cancer inhibiting drugs of CDK2 protein. The amino acid Val83 of CDK2 protein was consistently binding to new chemical entities indicating that amino acid is crucial and responsible for its inhibition. Present findings suggested that compound 9h has 100% human oral absorption with highest Glide score -8.3kcal/mol whereas drug molecules have feebler binding capacity and less Glide score indicating that the synthesized new chemical entity as potential inhibitor for CDK2 protein.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

scholarly journals DESIGN AND SYNTHESIS OF NOVEL IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AND THEIR ANTI-BACTERIAL ACTIVITY

2018 ◽  
Vol 11 (8) ◽  
pp. 252 ◽  
Author(s):  
Pushpalatha Budumuru ◽  
Srinivasarao Golagani ◽  
Venkata Siva Satyanaryana Kantamreddi
Keyword(s):  
Antibacterial Activity ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Beta Subunit ◽  
Diffusion Method ◽  
Pyridine Derivatives ◽  
Standard Drug ◽  
Mass Spectral ◽  
Design And Synthesis ◽  
Relationship Of

Objective: The present study aims to synthesize a novel derivatives of Imidazo[1,2-a]pyridines and the compounds were evaluated for their antibacterial activity.Methods: A series of newly synthesized compounds were characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Fourier transform infrared, mass spectral analysis, and screened for their antibacterial activity by disc diffusion method. Molecular docking studies were performed with a bacterial beta subunit of DNA gyrase using Auto Dock 4.2.6, and the docked conformations were analyzed using visual molecular dynamics.Results: The structural activity relationship of the synthesized imidazo[1,2-a]pyridine derivatives was studied against Gram-positive and Gram-negative bacteria. Among the synthesized compounds N-benzyl-4-((2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl) acetamido)methyl) benzamide (9a) are possessing high activity against Bacillus subtilis. The zone of inhibition produced by the compound 9a is wider than that of remaining compounds used in this study.Conclusion: The synthesized compounds exhibited good antibacterial activity in comparison with standard drug streptomycin. This suggests that the compound 9a and its analogs are exerting their activity by probably inhibiting bacterial beta subunit of DNA gyrase.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

Sign in / Sign up

Export Citation Format

Share Document