Synthesis and biological activity of novel Schiff bases derived from metronidazole

A number of novel Schiff bases (5a–i) and (7a–d) derived from metronidazole were synthesized. Reaction of 2-(2-methyl-5-nitro-imidazol-1-yl)-ethyl ester toluene-4-sulfonate with 4-hydroxybenzaldehyde and with 3-hydroxybenzaldehyde in the presence of a base afforded 4-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzaldehyde (5) and 3-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)benzaldehyde (7), respectively. The reaction of aldehydes 5 and 7 with a number of primary aromatic amines produced Schiff bases 5a–i and 7a–d, respectively. Structures of these compounds were confirmed through different spectroscopic methods such as ¹H-NMR, ¹³C-NMR, mass spectrometry, and also by elemental analyses. The prepared compounds were evaluated in vitro for their antigiardial, anti-trichomonal, antibacterial, and antifungal activities. Compounds 5e, 5g, 5i, 7a, 7b, 7c, and 7d exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC₅₀ of 7.2, 3.3, 1.5, 5.8, 4.5, 2.9, and 3.8 µg/mL, respectively. Compounds 5a and 5c also exhibited antigiradial activity with similar IC₅₀ values compared to the reference drug metronidazole with IC₅₀ of 7.2 µg/mL. The other compounds 5b, 5d, 5f, and 5 h also showed antigiardial activity but with higher IC₅₀ compared to the reference drug. Compounds were also tested for their anti-trichomonal activity, they, however, exhibited higher IC₅₀ compared to the reference drug metronidazole (7.4 µg/mL), except for compound 5a which exhibited anti-trichomonal activity with an IC₅₀ of 6.3 µg/mL. On the bases of preliminary screening, the newly synthesized compounds exhibited moderate to potent antimicrobial activities. Compound 5e inhibited the growth of Methicillin resistant Staphylococcus aureus (MRSA) and Bacillus cereus and compound 5c inhibited Candida Pathogenic fungus at 50 μg/mL compared with the positive control (Nystatin) which inhibits Candida at 25 μg/mL.     

Synthesis and anticonvulsant activity of novel quinazolin-4(3H)-one derived pyrazole analogs

Eighteen novel 6,8-(dibromo/unsubstituted)-2-(methyl/phenyl)-3-(4-(5-(substitutedphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl)phenyl)-quinazolin-4(3H)-ones 4a–4r were designed and synthesized in good yield. Antiepileptic screening of the title compounds was performed using MES and scPTZ seizures tests while the neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 4d, 4e, 4p, 4q, and 4r were found active in MES model, while 4a, 4d, 4f, 4m, and 4p showed significant antiepileptic activity in scPTZ model. Further, all these eight compounds were administered to rats and compounds 4e, 4p, and 4q showed better activity than Phenytoin in oral route. Among these compounds 4p revealed protection in MES after i.p. administration at a dose of 30 mg/kg (0.5 h) and 100 mg/kg (4 h). The compound 4p also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).     

Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline

The practice of medicinal chemistry is devoted to the discovery and development of new agents for treating disease. A new derivative of methyl 2-((E)-3-(3,4-dihydroxyphenyl)acrylamido)benzoate 2 was synthesized by reacting the amino group of methyl anthranilate 1 with caffeic acid in the presence of PCl₃. Cyclcondensation of 2 with hydrazine hydrate afforded the corresponding 2,3-dihydro-2-(3,4-dihydroxyphenyl) pyrazolo[5,1-b]quinazolin-9(1H)-one 3. The median lethal doses (LD_50s) of compounds 2 and 3 in mice were 1,135 and 495 mg/kg b.w., respectively. The anti-inflammatory, reducing power, chelating activity on Fe²⁺, free radical-scavenging, and total antioxidant activities were more pronounced in compound 2 compared to compound 3. On the other hand, antipyretic activity was more pronounced in compound 3 compared to compound 2. Antioxidant activity of compounds 2 and 3 increased with increased concentrations. Total antioxidant activity of compounds 2, 3 and both standards decreased in the order of α-tocopherol > compound 2 > trolox > BHA > BHT > compound 3. Administration of compounds 2 and 3 orally to the rats at dose of 50, 100, and 150 mg/kg b.w., for 10 days showed non-significant changes in serum level of GOT, GPT, ALP, γ-GT, and LDH as compared with the control group. In addition, oral administration of the compound 2 at a concentration of 100 and 150 mg/kg b.w. and compound 3 at a concentration of 150 mg/kg b.w. daily to normal rats for 10 days showed a significant increase in liver GSH, GPx, GR, and GST activities and significant decrease in TBARS level. But, administration of diclofenac sodium (30 mg/kg b.w.) orally to the rats daily for 10 days to rats showed significant increase in serum SGOT, SGPT, ALP, γ-GT, and LDH and significant decrease in liver GSH, GPx, GR, and GST activities. These findings suggest that compounds 2 and 3 exhibited good antioxidant and anti-inflammatory activity and also showed effects on liver enzymes.     

Synthesis,biological evaluation of certain pyrazolo[3,4-d]pyrimidines as novel anti-inflammatory and analgesic agents

In the present study, a series of pyrazolo[3,4-d]pyrimidin-4(5H)-ones linked at 5-position to thiazoline or thiazolidinone ring systems through imino linkage (5–8) was designed and synthesized. The compounds were assessed for their anti-inflammatory activity and analgesic in vivo. Also, their ability to inhibit ovine COX-1/COX-2 isozymes was evaluated using in vitro cyclooxygenase (COX) inhibition assay. The newly synthesized compounds 7, 8d, and 8e showed potent anti-inflammatory and analgesic activity. Moreover, compound 7 displayed preferential COX-2 inhibitory potency (IC₅₀ = 0.53 µM and COX-2 selectivity index = 10.07) which is more potent than the standard drug meloxicam. Interestingly, the tested compounds showed excellent gastrointestinal safety profile and were well tolerated by experimental animals with high safety margins than the reference drug meloxicam.     

Acylated phenylethanoid glycosides,echinacoside and acteoside from Cistanche tubulosa,improve glucose tolerance in mice

Acylated phenylethanoid glycosides, echinacoside (1) and acteoside (2), principal constituents in stems of Cistanche tubulosa (Orobanchaceae), inhibited the increase in postprandial blood glucose levels in starch-loaded mice at doses of 250–500 mg/kg p.o. These compounds (1 and 2) also significantly improved glucose tolerance in starch-loaded mice after 2 weeks of continuous administration at doses of 125 and/or 250 mg/kg/day p.o. without producing significant changes in body weight or food intake. In addition, several constituents from C. tubulosa, including 1 (IC₅₀ = 3.1 μM), 2 (1.2 μM), isoacteoside (3, 4.6 μM), 2′-acetylacteoside (4, 0.071 μM), tubulosides A (5, 8.8 μM) and B (9, 4.0 μM), syringalide A 3-O-α-l-rhamnopyranoside (10, 1.1 μM), campneoside I (13, 0.53 μM), and kankanoside J₁ (14, 9.3 μM), demonstrated potent rat lens aldose reductase inhibitory activity. In particular, the potency of compound 4 was similar to that of epalrestat (0.072 μM), a clinical aldose reductase inhibitor.     

Synthesis and anti-HIV-1 screening of novel N′-(1-(aryl)ethylidene)-2-(5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(1H)-yl)acetohydrazides

A novel series of N′-(1-(aryl)ethylidene)-2-(5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(1H)-yl)acetohydrazides was synthesized. The synthesis was carried out by thermal method as well as ultrasonic bath to reduce reaction time and to enhance product yields. The synthesized compounds were characterized by spectroscopic techniques like NMR, infrared and EIMS. The structure of compound 5w was elucidated by X-ray crystallography. The titled compounds were evaluated for anti-human immunodeficiency virus type 1 (anti-HIV-1) and cytotoxic activities. Biological studies indicated that amongst these compounds, 5a, b, j, h and i showed the activity with median effective concentration (EC₅₀) values less than 20 μM. Compound 5i exhibited the most potent anti-HIV-1 activity (EC₅₀ = 3.2 μM) while 5h showed anti-HIV-1 activity (EC₅₀ = 3.8 μM) with no toxicity at all in primary human lymphocytes, CEM and VERO cells.     

Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity

A new series of quinazoline analogs was designed, synthesized, and evaluated for their anticonvulsant activity. Compounds 6, 12, 21, 36, 37, and 38 showed 70–100 % protection against PTZ-induced seizures acting as GABA_A receptor agonists. Compound N-(3,4,5,6-tetrachloro-phthalimido)-2-[(3-phenyl-4-oxo-6-methyl-3H-quinazolin-2-yl)-thio]acetamide (12) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4H)-yl]-isoindoline-1,3-dione (38) representing the remarkably active compounds in this stud, showed ED₅₀ values of 457 and 251 mg/kg; TD₅₀ values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD₅₀ values of 1,288 and 1,380 mg/kg, and TI values of 2.82 and 5.50, respectively. Compound 38 proved to be almost twofold more active than the standard drug sodium valproate.     

Synthesis and evaluation of anticonvulsant and antidepressant activities of 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives

Seventeen 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives were synthesized, and their anticonvulsant and antidepressant activities were evaluated in a mouse model. The anticonvulsant effect and neurotoxicity of the compounds were evaluated with a maximal electroshock test and a rotated test in mice, respectively. Most of the compounds had anticonvulsant activity; among the compounds studied, 7-(3-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3h) was found to be the most potent compound with a median effective dose (ED₅₀) value of 28.9 mg/kg and a protective index value of 15.8, possessing better anticonvulsant activity and higher safety than the marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound 3h was tested in pentylenetetrazole-induced seizures tests, and the results suggest that compound 3h exerts anticonvulsant activity through a GABA-mediated mechanism. Forced swimming test showed that at a dose of 40 mg/kg, five compounds have significant antidepressant activity, the most active compound was 7-(2-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3g), which decreased immobility time by 56 %.     

Design,formulation and evaluation of Azithromycin binary solid dispersions using Kolliphor series for the solubility and in vitro dissolution rate enhancement

The main purpose of this investigation is increasing of the solubility and dissolution rate of Azithromycin by solid dispersion technique using Kolliphor P 237, Kolliphor P 338 and Kolliphor P 407. Kolliphor (P 237, P 338 and P 407) in various properties by weight {(1:0.5), (1:1), (1:1.5) and (1:2)}, utilizing solvent evaporation method. Dissolution studies carried out in phosphate buffer with pH 6.0 according to US pharmacopoeia method. The drug release profiles were studied, so we found that the dissolution rate of the drug (by calculating the dissolution parameters) was significantly increase compared to pure drug, also solubility of physical mixtures as well as solid dispersions increased compared to the intact drug. For example solubility of the drug increased from 85–753 μg mL^?1 (for Kolliphor P 237; 8 times more). The best results were as follows: Kolliphor P 237 > Kolliphor P 338 > Kolliphor P 407. IR spectra revealed no chemical incompatibility between drug and polymer. Drug-polymer interactions were investigated using differential scanning calorimetry, powder X-ray diffraction and scanning election microscopy. The dissolution rate and solubility of Azithromycin solid dispersions was improved significantly using Kolliphor. In addition, the simplicity of this method is very effective and have been met the project objectives.     

Synthesis and antitumor properties of novel alizarin analogs

Series of novel hybrids of alizarin and diamide scaffold (3a–3h, 7a–7h) were designed and synthesized. In vitro antitumor activities of all compounds against HepG-2, CNE, Spca-2, Hct-116, and MGC-803 cell lines were evaluated, and employing standard MTT assay compared with commercial anticancer drug 5-fluorouracil (5-FU). Compounds 7b, 7c, 7d, and 7e showed relatively high cytotoxicity. Especially, compound 7c exhibited the best cytotoxicity against CNE cells with IC₅₀ 9.08 µM, which was even stronger than that of 5-FU. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The action mechanism of representative compound 7c was preliminarily investigated by flow cytometry, which indicated that the compound can induce cell apoptosis in CNE cells. Cell cycle analysis showed that compound 7c mainly arrested CNE cells in G1 stage. In addition, the binding properties of a model analog 7c to DNA were investigated by different methods (fluorescence, CD spectroscopy), and the results indicated that 7c showed a moderate preference for binding ct-DNA.     

Design, synthesis and biological evaluation of some novel benzylidene-2-(4-phenylthiazol-2-yl) hydrazines as potential anti-inflammatory agents

A series of substituted benzylidene-2-(4-phenylthiazol-2-yl) hydrazines (2a–q) have been synthesized, characterized and evaluated for their anti-inflammatory activity by carrageenin-induced hind paw edema (acute inflammation) and cotton pellet granuloma (chronic inflammation) methods in rats. In carrageenin-induced hind paw edema method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg^?1 body weight, p.o. showed excellent inhibitions (51.80–86.74 %) in between 1 and 4 h. Similarly, in cotton pellet granuloma method, compounds 2a, 2b, 2c, 2d, 2h, 2k and 2p at a dose of 20 mg kg^?1 body weight, p.o. inhibited the granuloma formation (71.71–90.19 % inhibition) which was comparable to that of standard drug, ibuprofen (90.36 % inhibition of paw volume at 3 h and 94.02 % inhibition of granuloma formation). Structure activity relationship studies showed excellent activity of the compounds containing electron withdrawing group (fluoro, chloro, bromo or nitro) in phenyl ring at C2 and/or C4 position of thiazole ring.     

In vitro cytotoxicity, antimicrobial, and metal-chelating activity of triterpene saponins from tea seed grown in Kangra valley, India

This study was undertaken to isolate and characterize saponins from seeds of Camellia sinensis. Four triterpene saponins S ₁ , S ₂ , S ₃ , and S ₄ were isolated by chromatography on silica (60–120 mesh), followed by purification on Sep-Pak C-18 columns. The chemical structures (S ₁ –S ₄ ) were elucidated on the basis of 1-D and 2-D NMR. All the saponins show broad-spectrum antifungal activity against Candida albicans, Issatchenkia orientalis, Aspergillus flavus, A. niger, A. ochraceous, A. parasiticus, A. sydowii, and Trichophyton rubrum. The most susceptible test fungus was T. rubrum inhibited at a minimum inhibitory concentration of 31.25 μg/ml by all the four saponins. Cytotoxicity of these saponins was evaluated by methyl thiazole tetrazolium and sulfo-rhodamine B assays. The saponins when tested against five human cancer cells lines, viz., OVCAR-5 (ovarian carcinoma cells), MCF-7 (human breast adenocarcinoma cells), PC-3 (human prostate cancer cells), Colo-205 (colorectal adenocarcinoma cells), and HL-60 (human promyelocytic leukemia cells) showed high cytotoxicity activity (99 %) by S ₁ and S ₂ on PC-3 cells at concentration of 100 μg/ml. Similarly, when these saponins were tested against human PBMCs by lymphocytes proliferation assay, none showed significant activity. S ₃ (IC₅₀ = 1.72 mg/ml) showed high metal-chelating activity at a concentration of 20 mg/ml.     

Synthesis, molecular modeling, and biological evaluation of 1,2,4-triazole derivatives containing pyridine as potential anti-tumor agents

There is an accumulating body of experimental evidences validating focal adhesion kinase (FAK) as a therapeutic target and offering opportunities for anti-tumor drug development. In present study, we sought to synthesize twenty-eight potential FAK inhibitors as anti-tumor agents based on 1,2,4-triazole skeleton. The bioassay assays demonstrated that compounds 3e and 6j showed the most potent activity, 3e inhibited the growth of HCT116 and HepG2 cell lines with IC₅₀ values of 8.17 and 7.04 μM, while compound 6j showed the most potent biological activity against HCT116 cell line (IC₅₀ = 1.99 μM). Besides, compound 6j also exhibited significant FAK inhibitory activity (IC₅₀ = 2.41 μM). The results of flow cytometry and western-blot assay demonstrated that compounds 3e and 6j possessed good anti-proliferative activity. Docking simulations were performed to position compounds 3e and 6j into the active site of FAK to determine the probable binding model.     

Synthesis of indole-2-hydrazones in search of potential leishmanicidal agents

Indole-2-hydrazones 3–30 were synthesized and evaluated for their antileishmanial activity. The compounds 24 (IC₅₀ = 1.86 ± 0.09 μM), 12 (IC₅₀ = 2.26 ± 0.16 μM), 23 (IC₅₀ = 3.81 ± 0.29 μM), 8 (IC₅₀ = 4.01 ± 0.32 μM), 17 (IC₅₀ = 4.89 ± 0.31 μM), 20 (IC₅₀ = 4.89 ± 0.26 μM), 3 (IC₅₀ = 5.12 ± 0.34 μM), 15 (IC₅₀ = 5.26 ± 0.26 μM), 6 (IC₅₀ = 6.16 ± 0.38 μM), and 21 (IC₅₀ = 6.18 ± 0.045 μM) showed better activities than standard pentamidine (IC₅₀ = 7.02 ± 0. 09 μM). Compounds 4, 5, 7, 9–11, 13, 16, 18, 19, 22, 25–28, and 30 displayed good activities. The compounds 14 and 29 were found to be inactive. The synthesized compounds were characterized by different spectroscopic techniques.     

Potential anti-tubercular and in vitro anti-inflammatory agents: 9-substituted 1,8-dioxo-octahydroxanthenes through cascade/domino reaction by citric fruit juices

A series of 9-substituted 1,8-dioxo-octahydroxanthenes, 3a–k were synthesized and evaluated for their anti-tubercular and in vitro anti-inflammatory potential. Compounds 3b, 3d, 3e, 3f, 3g, and 3k demonstrated their potential anti-tubercular activity at 0.4 μg/ml comparable to streptomycin and pyrazinamide (standard drugs) screened by Microplate Alamar Blue assay against Mycobacterium tuberculosis H37 Ra. Compounds 3j, 3e, 3f, and 3c showed good in vitro anti-inflammatory activity by the inhibition of enzyme MMP-2 75, 65, 70, and 60 % and inhibition of enzyme MMP-9 by 90, 70, 60, and 60 %, respectively by gelatin zymography on gel electrophoresis. Standard drug tetracycline (300 μg/ml) is used as positive control which showed 90 % inhibition. The percentage inhibition was determined by a gel documentation system. DMSO was used as solvent control which did not show any inhibition.     

Effects of the neuroactive steroid allopregnanolone on intracranial self-stimulation in C57BL/6J Mice

Rationale

The neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) has effects on reward-related behaviors in mice and rats that suggest that it may activate brain reward circuits. Intracranial self-stimulation (ICSS) is an operant behavioral technique that detects changes in the sensitivity of brain reward circuitry following drug administration.

Objective

To examine the effects of the neuroactive steroid allopregnanolone on ICSS and to compare these effects to those of cocaine.

Methods

Male C57BL/6J mice implanted with stimulating electrodes implanted into the medial forebrain bundle responded for reinforcement by electrical stimulation (brain stimulation reward (BSR)). Mice received cocaine (n?=?11, 3.0–30.0 mg/kg, intraperitoneal (i.p.)) or the neuroactive steroid allopregnanolone (n?=?11, 3.0–17.0 mg/kg, i.p.). BSR thresholds (θ ₀) and maximum (MAX) operant response rates after drug treatments were compared to those after vehicle injections.

Results

Cocaine and allopregnanolone dose dependently lowered BSR thresholds relative to vehicle injections. Cocaine was maximally effective (80 % reduction) in the second 15 min following the 30 mg/kg dose, while allopregnanolone was maximally effective (30 % reduction) 15–45 min after the 17 mg/kg dose. Neither drug had significant effects on MAX response rates.

Conclusions

The effects of allopregnanolone on BSR thresholds are consistent with the previously reported effects of benzodiazepines and alcohol, suggesting that positive modulation of GABA_A receptors can facilitate reward-related behaviors in C57BL/6J mice.     

Design and synthesis of 3-(4-chlorophenyl)-2-(2-(4-substituted)-2-oxoethylthio)quinazolin-4(3H)-one as antihistamine agents

A series of novel 3-(4-chlorophenyl)-2-(2-(4-substituted)-2-oxoethylthio)quinazolin-4(3H)-one was synthesized by the reaction of 2-(3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)acetyl chloride with various amines. The starting material, (3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)acetyl chloride was synthesized from 4-chloroaniline by a multistep synthesis. All the title compounds were tested for their in vivo H₁-antihistaminic activity on conscious guinea pigs at the dose level of 10 mg/kg using chlorpheniramine maleate as the reference standard. The results of the biological activity indicate that the test compounds protected the animals from histamine-induced bronchospasm significantly. Compound 3-(4-chlorophenyl)-2-(2-(4-methylpiperazin-1-yl)-2-oxoethylthio)quinazolin-4(3H)-one (1) emerged as the most potent compound of the series (71.13 % protection) when compared to the reference standard chlorpheniramine maleate (70.09 % protection). Interestingly, compound A1 shows negligible sedation (12 %) compared to chlorpheniramine maleate (32 %). Therefore, compound A1 can serve as the lead molecule for further development.     

Cytotoxic dibenzocyclooctadiene lignans from Kadsura coccinea

Three new dibenzocyclooctadiene lignans, kadusurain A–C (1–3), together with two known compounds kadsuphilin A (4) and B (5), were isolated from an EtOAc fraction of the 80 % acetone extract of Kadsura coccinea (Lem.) A. C. Smith. Their structures were established by 1D and 2D NMR techniques, and mass spectroscopy. Anti-proliferative effect of isolated compounds was evaluated against four human tumor cell lines (A549, HCT116, HL-60, and HepG2), and it was found that compound 1 exhibited significant antiproliferative effects with IC₅₀ values ranging from 1.05 to 12.56 μg/ml.     

Synthesis and biological evaluation of some N 4-aryl-substituted 5-fluoroisatin-3-thiosemicarbazones

A series of N ⁴-aryl-substituted 5-fluoroisatin-3-thiosemicarbazones 3a–3l was synthesized and evaluated for selected biological activities. The brine shrimp lethality bioassay was carried out to study their in vitro cytotoxicity potential and besides, their antifungal, phytotoxic and urease inhibitory effects were also investigated. Seven compounds i.e. 3a, 3d, 3f, 3g, 3h, 3j and 3k proved to be active in the brine shrimp assay, displaying promising cytotoxicity (LD₅₀ = 6.89 × 10^?5–2.79 × 10^?4 M). Amongst these, 3a and 3h were found to be the most active ones (LD₅₀ = 6.89 × 10^?5 and 9.79 × 10^?5 M, respectively). Compounds 3i, 3j and 3 k displayed moderate (40 %) antifungal activity against one or two fungal strains i.e. A. flavus and/or M. canis. In phytotoxicity assay, all the synthesized compounds, including the reference point 2m showed weak-to-moderate (15–70 %) activity at the highest tested concentration (500 μg/mL). In urease inhibition assay, compounds 3f, 3g and 3j proved to be the most potent inhibitors, demonstrating relatively a higher degree of enzymatic inhibition with IC₅₀ values ranging from 37.7 to 47.3 μM.     

Synthesis,molecular docking studies,and in vitro screening of barbiturates/thiobarbiturates as antibacterial and cholinesterase inhibitors

On the basis of observed biological activity of barbiturates/thiobarbiturates, a set of 13 hydrazinecarboxamide/hydrazinecarbothioamides derivatives were designed and synthesized in good to excellent yield with extensive structural characterization. These compounds were screened for antibacterial and cholinesterase inhibitory activities. Two of the compounds 1 and 2 showed moderate bactericidal activity. Compounds 10 and 4 were found to be the most active acetyl/butyryl cholinesterase inhibitor, respectively (AChEI; 10; IC₅₀ = 40.78 μM and BChEI; 4; IC₅₀ = 3.31 μM). In silico molecular docking studies were carried out to identify active interacting sites of drug and enzyme and to establish structure–activity relationships. When predicted cholinesterase binding energies were compared with the experimentally determined inhibitory concentrations (IC₅₀), most active compounds were also found to be the most favorable for binding. The binding scores of compounds 10 and 4 were ?10.2 and ?9.3 kcal/mol, respectively.