Thiosemicarbazide Derivatives Research Articles

Synthesis of some benzylidene thiosemicarbazide derivatives and evaluation of their cytotoxicity on U87, MCF-7, A549, 3T3 and HUVEC cell lines

Iron homeostasis is altered in tumours in response to a perturbation in the expression of iron-dependent proteins. Therefore, iron chelators make cancerous cells more vulnerable to iron deficiency. Compounds having thiosemicarbazide scaffold with the ability to metal complex formation have the potential to act as anticancer. A series of thiosemicarbazide derivatives were designed, synthesized successfully and their cytotoxicity was then tested on some cancerous as well as laboratory normal model systems by using colorimetric assay based on WST-1 reagent. According to the cytotoxicity results, some compounds showed high toxicity effect on both the cancerous and healthy cell lines. The results of toxicity assays on U87 and A549 cell lines showed the survivability less than 50 % at all concentrations higher than 10 ppm for all the synthesized compounds. The MCF-7 cell line exhibited approximately the same behaviour and had survivability less than 60 %. The 3T3 in compared with HUVEC cell line showed a completely different behaviour against the synthesized compounds and had survivability more than 50 %. The selectivity index was also measured and based on the study results it could be concluded that the cytotoxicity profile of the synthesized compounds on 3T3 cell line shows a significant difference, indicating a good anticancer effect of these compounds.

Expression of glutation enzymes in splenic tissue is influenced by thiosemicarbazide derivatives

The administration of new Schiff heterocyclic bases and their copper (II) complexes, thiosemicarbazide derivatives induces various influences on the activity of glutathione-dependent enzymes in splenic tissue. The selective action of the studied compounds on the expression of glutathione enzymes is evident, which is manifested by a tendency of insignificant decrease of glutathione reductase (GR) and glutathione peroxidase (GPO), insignificant increase of glutathione-S-transferase (GST) and marked depression of glutaredoxin levels. The slight increase of GST under the action of the studied compounds can be considered as a protective reaction aimed at stagnating the intensity of peroxide processes and supporting the activity of the glutathione cycle, and decreased the activity of glutaredoxin denotes their antiproliferative, cytostatic effect. Further studies are needed to evaluate the mechanisms of action of the investigated compounds on the activity of glutathione-dependent enzymes in other biosystems and animal experiments, to assess the practical importance of the obtained results.

Synthesis, Characterization, and Investigation the Inhibitory Impact of Thiosemicarbazide Derivative toward the Corrosion of Mild Steel in Acidic Media

In this study we focused on the determination of influence the novel synthesized thiosemicarbazide derivative "2-(2-hydroxy-3-methoxybenzylidene) hydrazinecarbothioamide" (HMHC) influenced the corrosion inhibition of mild steel (MS) in a 1.0 M hydrochloric acid acidic solution.This is in an effort to preserve the metal material by maintaining it from corrosion.The synthesized inhibitor was characterized using elemental analysis, and NMR-spectroscopy. Then the corrosion inhibition capability of (HMHC) was studied on mild steel in an acidic medium by weight loss technique within variables [temperature, inhibitor concentration, and time]. The immersion periods were [1:00, 3:00, 5:00, 10:00, 24:00, and 72:00] hours and the temperature range was (303-333) K. Various concentration of (HMHC) were used and the immersion periods were [0.00, 0.001, 0.05, 0.10, 0.15, 0.20, 0.25, and 0.50] g/L. The prepared derivative has shown the ability to inhibit corrosion. It has been observed that the rate of erosion decreases with the increasing concentration of the prepared inhibitor and increases with the increasing temperature of the solution. The most promising inhibitor action is at 0.5 g/L with an inhibition efficiency of 90.2%. Where it found that the adsorption process of HMHC obeys the Langmuir isotherm model. The electronic properties of the HMHC molecules were obtained from density function theory (DFT) quantum chemical approach. The experimental approach and theoretical results were found to have impressive correlations.

Synthesis and Structural Studies of N-Maltosylated Aryl Thiobiurets

The derivatives of urea, thiourea and thiosemicarbazide play an important role in medicinal chemistry by influencing various pharmacological activities. The design and development of novel N-maltosides have emerged as an important class of organic compounds. A series of 1-hepta-O-benzoyl-β-D-Maltosyl- 5-aryl-2-4-thiobiurets are described in present work. By mixing hepta-O-benzoyl→D-maltosyl isocyanates with various aryl thiocarbamides, 1-hepta-O-benzoyl-β-D-maltosyl-5-aryl-2-4-thiobiurets have been synthesized. The identities of this newly synthesized 1-hepta-O-benzoyl-β-D-Maltosyl-5- aryl-2-4-thiobiurets were characterized by IR, 1H NMR and mass analyses. The compounds tested for antibacterial activity against a wide range of microorganisms, including Staphylococcus aureus, Escherichia coli, Psudomonas aeruginosa and antifungal activities against Aspergillus niger and Trichoderma. TLC confirmed the activity of these compounds.

Supramolecular Aggregation of Lead(Ii) Perchlorate and a Thiosemicarbazide Derivative Linked by a Myriad of Non-Covalent Interactions

Supramolecular Aggregation of Lead(Ii) Perchlorate and a Thiosemicarbazide Derivative Linked by a Myriad of Non-Covalent Interactions

SYNTHESIS, SPECTRAL ANALYSIS, ANTIBACTERIAL ACTIVITY AND MOLECULAR DOCKING STUDIES OF SOME NOVEL DERIVATIVES OF COMBINED TETRAZOLE AND THIOSEMICARBAZIDE MOIETIES

A few novel tetrazolyl thiosemicarbazide derivatives namely, 1-(1-(1-aryl-1H-tetrazol-5-yl)ethylidene) thiosemicarbazides (5a-5g) were synthesized and their structures were confirmed by FT-IR, 1H-NMR and 13C-NMR studies. The synthesized compounds were screened against various microbial strains for their antimicrobial activities and the results shows good activities. The compounds 5b and 5f were showing promising activity against Staphylococcus aureus and Escherichia coli. Additionally, Molecular docking studies were also carried out for these Tetrazolylthiosemicarbazide derivatives and were docked against Enoyl-[acyl-carrier-protein] reductase of Staphylococcus aureus (saFabI), obtained from Protein Data Bank (4ALI) as this structure was resolved in complex with NADP and triclosan. From the docking results, the compounds 5b, 5d and 5f are found to be strong binders with saFabI and having stronger binding affinity with saFabI than triclosan-saFabI complex. Therefore, it can be inferred that tetrazolylthiosemicarbazide derivatives, in specific, compounds 5f, 5b and 5d could be taken up for further evaluation towards novel drug design against Staphylococcus aureus.

Synthesis and analytical applications of thiosemicarbazide derivative

1-(4-tert-butylphenyl)4-(4-trifluoromethylphenyl)carbonylthiosemicarbazide (OBS) and was synthesized by reaction of 4-tert-Butylbenzoic hydrazide with 4-(trifluoromethyl)phenylisothiocyanate. The influence of many metal cations on the spectroscopic properties of the synthesized compound was investigated in dmso-water (1:1) by means of emission spectrometry.The influence of a series of metal ions including Cu2+,Co2+ , Al3+,Cr3+,Fe3+, Pb2+, Ni2+, Cd2+, Zn2+,Ag+ , Ba2+ , Mo3+, Se,Ca2+,Sn4+,Sb3+,Na+, K+,Li+,Sc3+, Sr2+, As3+, Be2+ and Mg2+on the spectroscopic properties of the ligand was investigated by means of emission spectrometry.The compounds were selectively complexed with Fe3+among many metal ions. The complex stoichiometry and the stability constant were determined by fluorimetric measurements. The ligand having thiosemicarbazide (OBS) showed sensitivity for Fe3+ ion with a linear range between 0.5 and 5.5 mg/L. The new method was applied in the determination of iron in the the sandy-soil reference material. A modified Standard addition method was used to remove the matrix effect.Detection and quantification limits were 0.07 and 0.214 mg/L, respectively.The simple and cost-effective method can be applied to soil samples.

DNA interaction perspectives of sulphur containing Knoevenagel condensed copper(II) complexes: Molecular docking, DFT, anti-biogram and insilico assessment

The present work describes the synthesis of a few novel Knoevenagel condensed copper(II) complexes from Schiff bases of thiosemicarbazide derivatives. The synthesized compounds have been characterized by various analytical and spectral techniques. The DFT calculations were carried on these compounds using Gaussian 09 W software which theoretically confirmed the change in UV–Vis electronic transitions after complexation. Interestingly, optimization and DFT calculations corroborated the stability and biological approachability of these copper complexes. Also, pharmacokinetic properties of the synthesized compounds have been computed using SWISS ADME online software which theoretically supports the oral mode of administration of the drug and its lead like activity. Moreover, all the copper complexes have the ability to undergo intercalative binding with CT-DNA, which has been confirmed by UV absorption studies, viscosity measurements, CV studies and molecular docking.

Erythrocytic antioxidant system in the administration of new coordination compounds thiosemicarbazide derivatives

Background: Currently, there is a growing interest in new local coordination compounds (CC), which demonstrated antitumor properties, but their influence on the erythrocyte antioxidant system has not been studied. The aim of the study: to study the effects of CC, thiosemicarbazide derivatives –TIA-160, CMT-67 and CMJ-33 on indices of the antioxidant system indicators in erythrocytes peripheral blood in vivo experiments. Material and methods: The action of CC on superoxide dismutase, catalase, total antioxidant capacity was evaluated on a group of 34 white rats, randomly divided into 4 groups: the first control group was injected subcutaneously with saline. The other groups (2 – TIA-160, 3 – CMT-67 and 4 – CMJ-33) were given subcutaneously 3 times a week for 30 days, 0.1µM / kg CC. Results: It was established that the TIA-160 compound demonstrated the highest capacity to induce the expression of erythrocyte catalase that exceeded the control level of 1.8, which did not correlate with the enzymatic superoxide dismutase (SOD) activity. Thus, this study showed that there are differences in the mechanisms of action of thiosemicarbazone derivatives. Conclusions: The influence of tested CC on the indices of the antioxidant system is selective. This selectivity may be the base to their strong selective antiproliferative and cytotoxic action on tumor cells, but not on healthy ones.

Regioselective formation of new 3-S-alkylated-1,2,4-triazole-quinolones

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography. Highlights Synthesis of novel quinoline-2-one/1,2,4-triazole hybrids in four steps. NMR, IR and mass spectra together with elemental analysis and X-ray crystallography proved the structure of 3-S-alkylated-1,2,4-triazole-quinolones and excluded the formation of 2-N-alkylated-1,3,4-thiadiazole-quinolones. Plausible mechanism for the formation of the targeted compounds was suggested.

Synthesis, spectral characterization, antimicrobial evaluation and molecular docking studies of new Cu (II), Zn (II) thiosemicarbazone based on sulfonyl isatin

Reaction of 5-(morpholinisulfonyl)isatin (1) with thiosemicarbazide derivative appended the corresponding thiosemicarbazone derivative 3 that further coordinated with copper and zinc acetate to afford copper and zinc complexes 4 and 5, respectively. The structure of the ligand and its two complexes Cu (II) and Zn (II) are confirmed using elemental analysis, molar conductance, spectra data (FT-IR, 1H NMR, 13C NMR, mass spectra), and thermogravimetric analysis (TGA). The ligand bounds to metal complex as neutral tridentate (ONS) donor with tetrahedral geometry structure. Additionally, the ligand forms two five-member rings with metals via carbonyl of isatin derivative, the nitrogen of azomethane (C=N), and sulpher of thiosemicarbazone. The antimicrobial activity was evaluated against two Gram-positive, two Gram-negative bacteria, and one fungal strain. Both complexes revealed antimicrobial activity against the tested strains. In addition, the result exhibited that the zinc complex 5 displayed higher activity than copper complex 4, where the zinc complex 5 showed an inhibition zone between (18 ± 0.20 and 23 ± 0.31) mm and activity index ranged between (84 and 100%) compared with Tetracycline. Moreover, the zinc complex 5 exhibited MIC (24.59–98.42 µM) in comparison to Tetracycline (35.14–140.62 µM). Finally, the in silico molecular docking study for thiosemicarbazone derivatives 3, 4, and 5 were carried out inside five active sites as an antibacterial targets. Among them, the ligand and its metal complexes showed the lower binding affinity and suggested that these derivatives 3, 4, and 5 may possibly be DHFR and topoisomerase IV inhibitors.

Sonochemical synthesis of the novel 1D zig-zag Hg(II)-Iodo bridged metal-organic coordination compounds with thiosemicarbazide derivative ligand

In the present research, a novel mercury (II) metal organic coordination compound, [Hg(Q)I2]n (Q = pyridine-4-carbaldehyde thiosemicarbazide) with nano rods shape was prepared applying an ultrasonic manner. The synthesized compound was determined with infrared spectroscopy (IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In solid-state, the coordination polymer takes the appearance of a zig-zag 1D polymer. The coordination number of Hg (II) is four by one sulfur atom of organic ligand and three iodine atoms which two of iodine atoms are coordinated to other repeating units, and one of iodine is unattached. The zig-zag 1D chains interact with neighboring chains via weak interactions, making a 3D supramolecular metal organic polymer. It was found that using high-intensity ultrasound is a facile, versatile, and eco-friendly synthetic instrument for supramolecular coordination compounds. Also, types of non-covalent interactions in the structure cause extraordinary flexibility to perform secondary interactions and create the property of attracting guests to this host.

Synthesis, characterization, DFT calculation, antioxidant activity, ADMET and molecular docking of thiosemicarbazide derivatives and their Cu (II) complexes

In this work, new thiosemicarbazides (ECA-1, ECA-2) and their Cu (II) complexes (ECA-1-Cu, ECA-2-Cu) were synthesized and their structures were characterized by 1H NMR, 13C NMR, FT-IR, LC-MS, UV–Vis, and thermogravimetric analysis methods. Also, the surface morphology of the all compounds were examined by SEM (Scanning Electron Microscope). In the second stage, in vitro antioxidant capacity of the obtained compounds was investigated. The evaluation of the antioxidant properties of both synthesized ligands and complexes in this study was carried out by DPPH and FRAP methods. According to the results, both complexes exhibited more antioxidant capacity than the corresponding ligands. When antioxidant effects are compared for DPPH (SC50 = 5.27 ± 0.05 μM) and for FRAP (7845.69 ± 16.75 mmolTE/g), compound ECA-2-Cu appears to have the best inhibition effect. The complexes were found non-electrolytic in nature with melting point of above 250 °C, and electronic spectra and magnetic behavior demonstrated that the complexes were found to be tetrahedral geometry. Further, in silico the ADMET properties which studies are a significant role in improving and predicting drug compounds were calculated using web-based platforms. The theoretical calculations were made using the method of Density Functional Theory (Frontier molecular orbital analyze and Nonlinear optical properties). Also, molecular docking studies were performed to evaluate the binding interactions between the ligand and complex compounds and Human Peroxiredoxin 2. Both in vitro and in silico results indicated that synthesized compounds could act as potent antioxidant agents.

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity.

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives’ applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and 1H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis.

Case Study in a Conceptual DFT Investigation of New Corrosion Inhibitor

Inhibition efficiency of thiosemicarbazide derivative, namely 4-ethyl-1-(4-oxo-4-phenylbutanoyl)thiosemicarbazide (EOPT) on corrosion of mild steel, was investigated utilizing the density functional theory (DFT) modeling techniques in the aqueous phase. Chemical parameters at the quantum level, such as energies of highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), dipole moment (µ), absolute electronegativity (χ), global hardness (η), softness (σ), and the fraction of electrons transferred (∆N) have been determined at the B3LYP level of theory with 6-31G (d, p) basis set.

SYNTHESIS OF 1-ACYL-4-METALLYL-THIOSEMICARBASIDES WITH LONG ALKYL SUBSTITUENTS

Thiosemicarbazide derivatives are increasingly attracting the attention of scientists due to their diverse biological activity. For example, substituted thiosemicarbazides are potent α-glucoxidase inhibitors, have antihelmintic action, as well as antituberculosis, antioxidant, and antimicrobial activity. Many metal complexes based on thiosemicarbazide-containing ligands exhibit antimicrobial properties. In addition, polysubstituted thiosemicarbazide derivatives are widely used in preparative organic chemistry as starting materials for the synthesis of heterocyclic compounds.
 This paper describes the method of production and physicochemical properties of five new 1-acyl-4-methyl-thiosemicarbazides. The synthesis was performed by the interaction of acid hydrazides with methyl isothiocyanate in ethanol under heating. The structure of the obtained compounds was confirmed based on 1H NMR spectroscopy data. The corresponding spectra were recorded in a solution of deuterated dimethyl sulfoxide on a Varian VXR 400 instrument.
 The PMR spectra of 2-R-N-methallylhydrazine-1-carbothioamides clearly indicate the introduction of a methallyl fragment. Thus, there is a doublet of the CH2NH group at 4.02 ppm. It is noted that the signal of the methylidene group of the methallyl fragment is manifested in the PMR spectrum in the form of a singlet at 4.73 ppm with a relative intensity of 2, as opposed to the expected splitting into two singlets with relative intensities of 1. A singlet with a relative intensity of 3 at 1.65 ppm corresponds to the methyl group of the methallyl fragment. Also, it can be clearly tracked the signals of the heptyl chain in the PMR spectrum (R = C7H15). Thus, the signals of the α-methylene and β-methylene groups are manifested in the form of a triplet at 2.12 ppm and a multiplet at 1.50 ppm, respectively. The terminal methyl group of the heptyl chain is manifested in the form of a triplet at 0.86 ppm with a relative intensity of 3. The signals of the other four methylene groups of the heptyl chain overlap and form a widened multiplet in the range of 1.25–1.29 ppm with a relative intensity of 8. Thus, in this work, the synthesis of new 1-acyl-4-methallyl-thiosemicarbazides with alkyl substituents was performed, and the 1H NMR spectra of the obtained compounds were analyzed.
 The obtained compounds are promising for use in synthetic organic chemistry (for the production of heterocyclic compounds), as well as ligands for the synthesis of complexes that will have biological activity.

Design and antiproliferative and antioxidant activities of furan-based thiosemicarbazides and 1,2,4-triazoles: their structure-activity relationship and SwissADME predictions

Due to the limited number of drugs in current clinical use, the diverse biological applications of furan have encouraged the preparation of a wide variety of thiosemicarbazide and triazole derivatives for the purpose of developing new drug agents. This study aimed to investigate the antiproliferative and antioxidant activities of thiosemicarbazides (1–12) and 1,2,4-triazoles (13–24). Out of the synthesized target compounds, 3, 4, 6, 7, 8, 9, 10, 11, 12, 15, 16, 18, 19, 20, 21, 22, 23, and 24 are novel while the synthesis of the remaining compounds is present in the literature. Compound 15 (IC50: 8.81 ± 0.28 µM) showed the highest antiproliferative activity against the cervical (HeLa) cancer cell line among the compounds. In the lipid peroxidation inhibitory activity, thiosemicarbazide derivatives 3, 10, and 9 showed highest activity with IC50 of 21.80 ± 0.69, 26.49 ± 0.61, and 29.07 ± 0.52 µM, respectively, while triazole derivatives 15, 18, 19, 20, 21, and 22 exhibited the highest activity. Moreover, physicochemical properties, pharmacokinetic properties, and drug-likeness of all synthesized products were calculated using SwissADME. In addition, the effect of the structure–activity relationships of the 1,2,4-triazole derivatives (13–24) on the results of antiproliferative and antioxidant activity assays was evaluated.

Synthesis and Antinociceptive Effect of Some Thiazole-Piperazine Derivatives: Involvement of Opioidergic System in the Activity

In this study, we aimed to design and synthesize novel molecules carrying both the thiazole and piperazine rings in their structures and to investigate their antinociceptive activity. Targeted compounds were obtained by reacting thiosemicarbazide derivative and appropriate 2-bromoacetophenone in ethanol. The structures of the obtained compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). Experimental data from in vivo tests showed that test compounds 3a–3c, 3f, and 3g (50 mg/kg) significantly prolonged reaction times of animals in tail-clip and hot-plate tests compared to the controls, indicating that these compounds possess centrally mediated antinociceptive activities. Furthermore, these compounds reduced the number of writhing behaviors in the acetic acid-induced writhing tests, showing that the compounds also possess peripheral antinociceptive activity. In the mechanistic studies, naloxone pre-treatments abolished the antinociceptive activities of compounds 3a–3c, 3f, and 3g, indicating that opioidergic mechanisms were involved in their antinociceptive effects. Molecular docking studies demonstrating significant interactions between the active compounds and µ- and δ-opioid receptor proteins supported the pharmacological findings. This study is the first showing that molecules designed to bear thiazole and piperazine moieties together on their structure exert centrally and peripherally mediated antinociceptive effects by activating the opioid system.

Synthesis and antiviral evaluation of 5-(arylazo)salicylaldehyde thiosemicarbazone derivatives as potent anti-bovine viral diarrhea virus agents

Thiosemicarbazones which previously characterized as a new class that inhibit anti-bovine viral diarrhea virus (BVDV) prompted us for synthesizing a series of new thiosemicarbazone derivatives. Thus, in this study, we reported the synthesis and antiviral evaluation of a series of 5-(arylazo)salicylaldehyde thiosemicarbazone derivatives for their expected antiviral activity. The desired products were synthesized from the condensation of 5-(arylazo)salicylaldehyde derivatives with N-(4)-substituted thiosemicarbazide derivatives. Antiviral screening was performed to test the anti-bovine viral diarrhea virus properties. From the obtained results, compounds 5, 23 and 24 showed highly selective activity against BVDV by blocking the viral RNA synthesis in cell culture. The BVDV in antiviral drug studies is valuable surrogate for the hepatitis C virus (HCV); so, the above results provided a novel candidate for the development of anti-HCV agents.

Design, Synthesis, Antimicrobial Evaluation and Molecular Docking Studies of Some Novel Monoterpenoids Substituted Quinoxaline Thiosemicarbazide Derivatives

Owing to the increasingly serious problems caused by multidrug resistance in acquired infection pathogens, it has become an urgent need to develop new classes of antibiotics for overcoming the resistance. The present study aims to increase the antimicrobial activity of quinoxaline thiosemicarbazide derivatives by introducing a hydrophobic alkyl chain, an electron-releasing group in the ring, and substitution by some acyclic, cyclic and bicyclic monoterpenes and their antimicrobial evaluation against various strains with molecular docking studies. The lead molecule (1E, 4E)-1-(7-chloro-3-isopropyl- quinoxalin-2(1H)-ylidene) thiosemicarbazide was synthesized and condensed with various monoterpenes to synthesize different derivatives. The structures of compounds were confirmed through IR., NMR & mass spectroscopy. The synthesized derivatives were evaluated in vitro for antibacterial and antifungal activities against various strains using the agar dilution method. Molecular docking studies of the derivatives (Va– Vg) were performed to find out essential binding sites against target protein (PDB: 3 FAP, receptor: FKBP 12) using Autodock 4.2. The compounds Va, Vd, Vf & Vg exhibited potent antibacterial and antifungal activity. Among all these compounds Vd was found to exhibit more potent activity against gram +Ve, gram –Ve bacterial and fungal strains at MIC 0.19 μg/ml, 0.39μg/ml, and 1.56 μg/ml respectively. The docking studies of all the compounds exhibit potent binding energy, but the compound Vd exhibit interactive binding energy (-9.98 kcal/mol) to the active pockets of the receptor FKBP12. The compound Vd interacting with various active sites of amino acids of receptors like PHE128, TRP190, TYR26, VAL55, ILE56, PHE99, and TRP59. In terms of structure- activity relationship study it is revealed that the activity profile against bacterial and fungal strains was altered by the formation of monoterpenoid substituted (1E, 4E)-1-(7- chloro-3-isopropylquinoxalin-2(1H)-ylidene) thiosemicar- bazide derivatives. The study reveals that bicyclic monoterpenes substituted compounds exhibit greater activity than cyclic and acyclic. The molecular docking studies also showed that all the compounds exhibit good docking energy to bind and inhibit the FKBP12 receptor.