313 © 2025 The Author(s). Published by College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License Synthesis, Characterization, Molecular Docking, and In Silico ADME Study for Some New Different Derivatives for Succiniohydrazide Asmaa A. Maryoosh1* and Oday H. R. Al-Jeilawi2 1Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, Iraq. 1,2 Department of Chemistry, College of Sciences, University of Baghdad, Baghdad, Iraq. *Corresponding Author. Received: 2 July 2023 Accepted: 27 August 2023 Published: 20 January 2025 doi.org/10.30526/38.1.3642 Abstract Many studies have found effective oral influenza virus inhibitors based on an aryl benzoyl hydrazide scaffold and antiviral. This study aims to prepare a new series of derivatives containing succinohydrazide as a precursor. In the first step, after synthesis of their precursor, it has been prepared di benzoyl succinohydrazide using a two-step process that involved reacting (o,m,p)-chloro benzoic acid with thionyl chloride to obtain freshly prepared substituted benzoyl chloride derivatives that were then reacted with succinohydrazide, or by a second method, directly reacting substituted benzoyl chloride with succinohydrazide to give benzoylsuccinohydrazide derivatives. After that, different derivatives were prepared involving the reaction of succinohydrazide with substituted benzene sulphonyl chloride, benzyl chloride, and phenacyl chloride. FTIR, 1HNMR, and 13CNMR spectra have been used to verify the structures of newly synthesized compounds. The Swiss ADME method with boiled egg prediction was used to analyze its pharmacokinetic properties. Then, genetic optimization of linkage docking (GOLD) was used in theoretical studies to investigate the binding mechanism of the protein-ligand produced with the protein (1SA0). Among all synthesis compounds, compound 2b has excellent results compared with colchicine and can be considered a good anti- bacterial against Escherichia coli and an anti-breast cancer drug. Keywords: ADME, benzohydrazide, benzylhydrazide, Lipinsky rule, molecular docking, sulfonohydrazide, 1. Introduction Microtubules (α,β-tubulin heterodimers) are essential components of eukaryotic cell structure and play important roles in a variety of cellular processes, including cell shape determination and repair, motility regulation, intracellular building organization, secretion, cellular transport, and https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0002-4970-6675 mailto:asmaa.Abd2105m@sc.uobaghdad.edu.iq https://orcid.org/0000-0002-4092-2072 mailto:Oday.h@sc.uobaghdad.edu.iq IHJPAS. 2025, 38 (1) 314 cell division (1,2). Microtubules have been identified as a viable target for chemotherapeutic drugs targeting breast cancer cells during the last three decades due to their critical roles in the cell's life cycle (3,4). Tubulin, a (α, β-heterodimer) first discovered as the cellular colchicine- binding protein, targets many small-molecule ligands that interact with microtubule dynamics and are therapeutically beneficial, notably in cancer therapy (5). Colchicine binding sites have been modified in terms of chemical structure and pharmacokinetic properties and examined to develop a highly effective, low-toxicity medicine for cancer treatment (6). Sulfonamide is one of the essential building blocks in organic chemistry, with numerous pharmaceutical and pharmacological agents exhibiting antibacterial, antibacterial, antitiviral, anti-obesity, anhydrase, HIV protease inhibitors, diuretics, antithyroid, antitumor, and anti-neuropathic pain activity (7,8). New oxadiazole-ringed sulfonamides may inhibit b-glucuronidase (9). Previously proven to have great potential, sulphonamides containing aliphatic moieties were synthesized and tested for their α-glucosidase, anti-urease, antibacterial, and antibacterial properties (10). In organic solvent-free water-based sulfonyl hydrazide synthesis, an equimolar amount of sulfonyl chlorides and hydrochlorides react at 60˚C for 1 hour in water with Et3N to form a series of substituted hydrazides (11). Many researchers have found effective oral influenza virus inhibitors based on an aryl benzoyl hydrazide scaffold and antiviral (12). Drug development, materials, and agrochemicals use benzylic derivatives. In environmentally friendly solvents, many methods produce benzylic derivatives on beneficial pharmaceutical molecules (13). Some benzyl derivatives are used as inhibitors of the corrosion of carbon steel in HCl and H2SO4 media (14,15). Some compounds from aryl sulfonylhydrazides and benzylic ammonium salts have good efficiency and simple handling (16). Aryl benzoyl hydrazide derivatives have been studied in silico as influenza virus antivirals, and these showed significant antiviral factors and antimicrobial agents (17,18). Lipinski's rule of five (Ro5) is used in drug development to predict if a bioactive molecule is orally bioavailable based on drug physicochemical features like absorption, distribution, metabolism, and excretion (ADME) (19). Early prediction of ADME parameters has been shown to significantly reduce the rate of pharmacokinetic failure in clinical phases during the design phase and determine if a compound has a chance to be a promising drug (20). GOLD refers to the "genetic method for docking flexible ligands into a protein binding site." It shows the optimum orientation for a ligand that links to a protein's active site (21,22). The "BOILED-Egg" predicts small molecule intestinal absorption and brain penetration (23). It estimates small molecules' lipophilicity, polarity, human intestinal absorption (HIA), and brain access (BBB) (20) and tests therapeutic candidate assessment (20). Drug-likeness, medicinal chemistry, ADME pharmacokinetics, and physicochemical features are connected to this model (22). This study aims to prepare a new series of derivatives containing succinohydrazide as a precursor. IHJPAS. 2025, 38 (1) 315 2. Materials and Methods 2.1. Instruments All chemical compounds were used without further purification and obtained from BDH, Fluka, Aldrich, and Merck companies. Thin-layer chromatography (TLC) was used on pre-coated Merck (Macherey-Nagel, Germany) silica gel 60-F plates with a layer thickness of 0.25 mm (Merck). A mixture of hexane 3:2 ethanol was used to develop the solvent system TLC eluent, and an ultraviolet lamp detected the spots. A molecular docking study was done at the College of Pharmacy /Al-Nahrain University. The melting points of the synthesized compounds were recorded using an electro-thermal melting point apparatus. The IR analysis was conducted using an FT-IR ALPHA II spectrometer (Bruker) at Mustansiriyah University/College of Science. NMR analyses were performed via 1H NMR at 500 MHz and 13C NMR at 125 MHz (VARIAN- INOVA). The solvent used was (DMSO-d6), and the internal reference was TMS. 2.2. Synthesis of succinohydrazide (1) Succinohydrazide was produced using previously reported methods and described [24] physical properties show in Table 1. FT-IR (υ, cm-1): 3306,3286 (NH2), 3180 (N-H), 2981,2875 (C- Haliph.), 1622 (C=Oamide); 1H NMR (H, ppm): 8.98 (2H, s, NH-C=O), 4.14 (4H, s, NH2), 2.61- 2.57 (4H, t, CH2); 13C NMR (C, ppm): 171.22 (C=O), 29.40 (CH2-CH2). 2.3. Synthesis of N'1,N'4-dibenzoylsuccinohydrazide (2a) and N'1,N'4-bis(4-methoxy benzoyl) succinohydrazide (2b) Succinohydrazide was put in a round bottom flask fixed in an ice bath (0.6 g, 4 mmol) with 15 mL of THF as a reaction solvent, and the mixture was homogenized using a magnetic stirrer. An (8 mmol) of (benzoyl chloride or p- methoxybenzoylchloride) was introduced dropwise with steady stirring at 0˚C for 1 hour. TLC checked the reaction, and when the reaction was done, it was neutralized by adding 5% sodium bicarbonate solution until it neutralized and was allowed to settle down. Finally, after filtering out the separated solid, the solid was washed with distilled water to obtain compounds (2a-b). Table 1 shows the physical properties (25). 2.3.1. N'1, N'4-dibenzoylsuccinohydrazide (2a) The FT-IR (υ, cm-1): 3192 (N-H), 3030 (C-Harom), 2933,2878 (C-Haliph.), 1692 (NHC=Oamide CH2),1667 (NHC=OamidePh), 1594,1573 (C=Carom.); 1H NMR ( H, ppm): 10.32 (2H, s, NH- C=OPh),9.96 (2H, s, NH-C=OCH2), 7.95–7.47 (10H, m, Ar-H), 2.56-2.51 (4H, t, CH2); 13C NMR ( C, ppm): 171.05 (NHC=OamideCH2),165.92 (NHC=OamidePh), 132.22-127.87 (Ar-C), 28.96 (CH2-CH2). 2.3.2. N'1, N'4-bis (4-methoxybenzoyl) succinohydrazide (2b) The FT-IR (υ, cm-1): 3208 (N-H), 3021 (C-Harom.), 2977,2844 (C-Haliph.), 1686 (NHC=Oamide CH2),1637 (NHC=OamidePh), 1606,1577 (C=Carom.) 1025,843 (p-sub.); 1H NMR ( H, ppm): 10.17 (2H, s, NH-C=OPh),9.89 (2H, s, NH-C=OCH2), 7.87–7.00 (8H, q, Ar-H), 3.81 (6H, s, OCH3), 2.61-2.54 (4H, t, CH2); 13C NMR ( C, ppm): 171.12 (NHC=OamideCH2),165.46 (NHC=OamidePh), 162.42-114.12 (Ar-C), 55.83 OCH3, 29.01(CH2-CH2). 2.4. Synthesis of N'1,N'4-bis(2-chlorobenzoyl)succinohydrazide (2c), N'1,N'4-bis(3-chloro benzoyl)succinohydrazide (2d), N'1,N'4-bis(4-chlorobenzoyl)succinohydrazide (2e) IHJPAS. 2025, 38 (1) 316 A 100 mL one-neck round bottom flask was attached to a reflux condenser (0.3 g, 2 mmol) of each different substituted chloro benzoic acid, then added (2.5 mL, 3 mmol) of thionyl chloride. The reaction was performed under reflux conditions for 3 hours to obtain the corresponding acid chloride. The excess of thionyl chloride was evaporated, and without separation, succinohydrazide (1) was added, followed by continuous reflux for (3-6) hours. Check the end of the reaction by TLC. The product (2c-2e) was obtained as crystals. Physical properties are shown in Table 1 (26). 2.4.1. N'1, N'4-bis (2-chlorobenzoyl) succinohydrazide (2c) The FT-IR (υ, cm-1): 3202 (N-H), 3081 (C-Harom.), 2929, 2855 (C-Haliph.), 1698 (NHC=Oamide CH2), 1622 (NHC=OamidePh), 1605, 1576 (C=Carom.) 1098,831 (o-sub.). 2.4.2. N'1, N'4-bis (3-chlorobenzoyl) succinohydrazide (2d) The FT-IR (υ,cm-1): 3207 (N-H), 3031 (C-Harom.), 2950,2870 (C-Haliph.), 1686 (NHC=OamideCH2), 1638 (NHC=OamidePh),1597,1570 (C=Carom.) 1138, 897 (m-sub.); 1H NMR (H, ppm): 10.47(2H, s , NH-C=OPh),10.04 (2H, s , NH-C=OCH2), 7.87 – 7.49 (8H, m, Ar-H), 2.57-2.53 (4H, t,CH2 ); 13C NMR (C, ppm): 170.98 (NHC=OamideCH2), 164.53 (NHC=OamidePh), 134.89-127.70 (Ar-C), 28.88(CH2-CH2). 2.4.3. N'1, N'4-bis (4-chlorobenzoyl) succinohydrazide (2e) The FT-IR (υ, cm-1): 3174 (N-H), 3048 (C-Harom.), 2922, 2850 (C-Haliph.), 1679 (NHC=Oamide CH2), 1639 (NHC=OamidePh), 1591,1573 (C=Carom.) 1091,850 (p-sub); 1H NMR (H, ppm): 10.39 (2H, s, PhNH-C=O), 9.96 (2H, s, CH2NH-C=O), 7.91 – 7.52 (8H, q, Ar-H), 2.82-2.47 (4H, t, CH2); 13C NMR (C, ppm):174.01(CH2NHC=Oamide),166.88 (PhNHC=Oamide), 138.23-129.21 (Ar-C), 29.23 (CH2-CH2). 2.5. Succinyl dibenzenesulfonohydrazide derivatives (3a-c) [10] A mixture of compound (1) (0.6 g, 4 mmol) and various substitutes (benzene sulphonyl chloride, p-bromo benzene sulphonyl chloride (1.047 mL, 8 mmol) in ethanol (25 mL), and a few drops of GAA were added and stirred for (10-15 min). In comparison, p-methylbenzene sulphonyl chloride (1.525 g, 8 mmol) in 25 mL ethanol and the addition of a few drops of GAA under reflux conditions for (30 min) led to the formation of a white precipitate with a good yield. The release of a gas that changes the color of the blue litmus paper to red was noticed, a checked completion reaction by TLC. The fine white powder was obtained after being filtered, dried, and recrystallized with n-hexane. Table 1 lists the physical properties. 2.5.1. N', N'''-succinyldibenzenesulfonohydrazide (3a) The FT-IR (υ, cm-1): 3206 (N-H), 3065 (C-Harom.), 2971, 2 927(C-Haliph.), 1688 (NHC=Oamide), 1583, 15 12(C=Carom.)1376, 11 62(SO2). 2.5.2. N', N'''-succinylbis (4-bromobenzenesulfonohydrazide) (3b) The FT-IR (υ, cm-1): 3289 (N-H), 3102 (C-Harom.), 2996, 2931 (C-Haliph.), 1665 (NHC=Oamide) 1601, 1577 (C=Carom.)1386,1174 (SO2) 1000,824 (p-sub); 1H NMR (H, ppm): 10.91 (2H, s, NH- SO2),9.78 (2H, s, NH-C=O),7.57–7.52(8H, q, Ar-H), 2.61-2.60 (4H, t, CH2); 13C NMR (C,ppm):170.92 (NHC=Oamide), 147.35-122.52 (Ar-C), 27.62 (CH2-CH2). IHJPAS. 2025, 38 (1) 317 2.5.3. N', N'''-succinylbis (4-methylbenzenesulfonohydrazide) (3c) The FT-IR (υ, cm-1): 3271 (N-H), 3060 (C-Harom.), 2979, 2860 (C-Haliph.), 1669 (NHC=Oamide), 1574, 1534 (C=Carom.)1362,1159 (SO2) 1007,811(p-sub); 1H NMR (H, ppm): 10.97 (2H, s, NH- SO2), 10.46 (2H, s, NH-C=O),7.50–7.11(8H, q, Ar-H), 2.63-2.59(4H, t, CH2 );13C NMR (C, ppm): 173.77 (NHC=Oamide), 138.79-125.94 (Ar-C), 28.13 (CH2-CH2) 21.22 (CH3). 2.6. Synthesis of dibenzyl succinohydrazide derivatives(4a-c) [27] with modification In a round-bottom flask, a mixture of compound (1) (0.6 g, 4 mmol) was added to 10 mL DMF with heating, and (1.11 mL, 8 mmol) from Et3N was added as a catalyst; (8 mmol) of benzyl chloride with a different substituent in DMF (10 mL) was added. After 15-25 hours of reflux, the mixture was poured over grinding ice and extracted with diethyl ether. The physical characteristics are detailed in Table 1. 2.6.1. N'1, N'4-dibenzylsuccinohydrazide (4a) The FT-IR (υ, cm-1): 3400 (N-H), 3033 (C-Harom.), 2978, 2882 (C-Haliph.), 1664 (NHC=Oamide), 1639, 1540 (C=Carom.). 2.6.2. N'1, N'4-bis (2-nitrobenzyl) succinohydrazide (4b) The FT-IR (υ, cm-1): 3391 (N-H), 3088 (C-Harom.), 2946, 2880 (C-Haliph.), 1668 (NHC=Oamide), 1623,160 (C=Carom.)1521, 1319 (NO2)1130, 743 (o-sub). 2.6.3. N'1, N'4-bis (4-nitrobenzyl) succinohydrazide (4c) The FT-IR (υ, cm-1): 3214 (N-H), 3073 (C-Harom.), 2968, 2887 (C-Haliph.), 1668 (NHC=Oamide), 1655, 1598 (C=Carom.)1510,1339 (NO2) 1106,850 (p-sub); 1H NMR (H, ppm): 9.01 (2H, s, NH- C=O), 5.35 (2H, s, NHCH2), 8.15–7.63 (8H, q, Ar-H), 4.13 (PhCH2), 2.74-2.71 (4H, t, CH2); 13C NMR (C, ppm): 170.99 (C=Oamide), 146.39-123.63 (Ar-C), 54.18 (PhCH2), 29.20(CH2-CH2). 2.7. Synthesis of N'1,N'4-bis(2-oxo-2-phenylethyl) succinohydrazide (5) (28). A mixture of compound (1) (0.3 g, 2 mmol) and phenacyl chloride (0.6 g, 4 mmol) in 15 mL of DMF in the presence of Et3N (0.55 mL, 4 mmol) was refluxed for 5 hours (According to TLC results). The mixture was put on grinding ice after the end of the reaction. The product is then extracted using diethyl ether in a separation funnel and dried. The physical properties of the compound are detailed in Table 1. FT-IR (υ, cm-1): 3124 (N-H), 3059 (C-Harom.), 2980, 2878 (C-Haliph.), 1717 (C=OKetone) 1686 (C=Oamide), 1640, 1595 (C=Carom.). IHJPAS. 2025, 38 (1) 318 Scheme1. Synthesis of derivatives (1-5). Table 1. Chemical formula, physical properties, and molecular weight of the synthesized compounds (1-5). No. Chemical structure Color Melting point (℃) Stirring/ reflux time reaction Yield (%) M.wt (g/mol) 1 bright white* 170-172 3 hr. Stirring 95 146.15 2a white 187-190 1 hr. stirring 85 354.37 2b white 210-213 0.5 hr. Stirring 88 414.42 2c Dark off white 183-186 9 hr. reflux 80 423.25 2d Dark off white 175-178 5.25 h. reflux 68 423.25 2e Dark off white 180-182 4 hr. reflux 75 423.25 IHJPAS. 2025, 38 (1) 319 *Literature (169-170) ℃)(24) 2.8. Computational study; molecular docking ADME analysis Molecular docking determines the optimal orientation of a ligand that binds to a protein's active site, and the ligand's affinity impacts its binding and interaction (18). The Protein Data Bank (PDB:1SA0) https://www.rcsb.org offered enzyme crystal structures for docking. Swiss ADME with BOILED-Egg predicted the synthesized compound's physicochemical characteristics and pharmacokinetics, which was designed to forecast the tendency of small compounds to be absorbed by the gastrointestinal system or to access the brain (29). Good ADME features make synthetic compounds drug-like (30). Following Lipinski's requirements, the rule created by Christopher Lipinski of Pfizer in 1997 specifies that an orally active medicine should have no more than one violation of the following conditions: (1) ≤ 5 hydrogen bonding donors, (2) hydrogen bonding acceptors ≤ 10 (3) Molecular weight shouldn't go above 500 m/z. (4) The lipophilicity (CLogP) ≤ 5 (25). Oral drugs have a lower M.wt. and fewer H-bond donors, acceptors, and rotatable bonds than injectable. Pulmonary medicines have greater PSA because pulmonary permeability is less susceptible to polar hydrogen-bonding functionality (22). Drug properties like intestinal absorption and brain access help estimate drug development phases. The 3a white 166-168 0.5 hr. stirring 75 426.46 3b white 318 dec. 0.25 hr. stirring 70 584.25 3c white >300 0.5 hr. reflux 80 454.52 4a Off white Gummy 15 reflux 60 354.37 4b orange Gummy 19 hr. reflux 69 416.39 4c orange 108-110 18 reflux 75 416.39 5 Pale yellow 101-104 5 reflux 56 382.42 IHJPAS. 2025, 38 (1) 320 brain or bowel penetration method and estimating tool are used. BOILED-Egg accurately predicts its small compound's adipogenesis and polarization (29). Predictions of each brain region are obtained depending on physical and chemical properties and immediately converted into the molecular design (20). The data obtained is shown in Table 2. 3. Result and Discussion 3.1. Chemistry As mentioned in the literature, succinohydrazide was prepared in this work. It was a precursor for synthesizing diverse derivatives by reacting with different organic compounds (benzoyl chloride, sulphonyl chloride, and phenacyl chloride). These reactions undergo the nucleophile- substitution mechanism. However, benzyl chloride reactions undergo an unimolecular nucleophilic substitution (SN1) mechanism. Steps The TLC technique monitored the synthesis of all these compounds, which was analyzed by FT-IR, 1H, and 13C NMR spectroscopy, as shown in Scheme 1. 3.2. Spectral analysis All spectra were interpreted by Silverstein Spectrometric Identification of Organic Compounds 7th Ed. (31). The existence of a secondary amine group was indicated by the absence of NH2 absorption in succinohydrazide 3305–3286 cm-1 and the appearance of N-H absorption in the range of 3400–3124 cm-1. In addition, in derivatives from 2a–2e, the absorption band between 1698–1664 cm-1 contains NHC=OamideCH2 and 1669–1622 cm-1 contains NHC=OamidePh, whereas in 3a–3c derivatives, the absorption band between 1688–1665 contains NHC=Oamide with the presence of two bands of SO2 between 1386–1362 and 1174–1159. 4a–4c illustrate the existence of NHC=OamideCH2 between 1668 and 1664 and are distinguished by the appearance of two strong bands, 1521–1510 and 1339–1319, corresponding to NO2. The bands observed in 1717 C=OKetone and 1686 C=Oamide are present in phenacyl derivative 5. The signal in the 1H NMR spectra for derivative 1 is 8.98 for NH-C=O and 4.14 for free NH2. Signals are seen at 10.47–10.17 ppm for NH adjacent to PhC=Oamide and 10.04–9.89 ppm for NH adjacent to CH2C=Oamid in 2a–2e. Furthermore, 3b and 3c show signals in 10.97, 10.91 for NH-SO2 and 10.46, 9.78 for NHC=Oamid, while 4c shows signals in 9.01 for NH-C=O, 5.35 for NH-CH2, and 4.13 for CH2-Ph. 13C NMR indicates signals in 171.12 to 170.98 ppm for CH2C=Oamid and 165.92 to 164.53 ppm for PhC=Oamide. Signals 173.77 and 170.92 for NH-C=O appear in sulphonyl derivatives 3b and 3c. Finally, 4c shows C=Oamid at 170.99 and Ph-CH2 at 54.18. As a consequence, the synthesis of derivatives is approved. 3.3. In silico pharmacokinetics ADME properties When synthesized compounds exhibit strong ADME qualities, they may be considered excellent candidates for drug-like properties. Oral bioavailability is more likely in molecules with five hydrogen bond donors HBD, ten hydrogen bond accepter HBA, a molecular weight< 500 g/mol, and a calculated Log P< 5 (20). Orally inactive compounds violate at least two of the Five Rules (32). The results in Table 2 indicate that all synthesis compounds 2a to 5 have no violations of Lipinski’s rule except for 3b, which was excluded from the molecular docking study according to the ADME result. It has one violation in M.wt. that exceeded 500 g/mol, and all Compounds IHJPAS. 2025, 38 (1) 321 2a to 5 have the highest docking scores by hydrogen bonds with the target protein (1SA0). The log shows no exceeding the normal range for any of the compounds. In the Lipinski rule of five, a score of 0.55 indicates strong bioavailability and permeability. It was estimated that the topological polar surface area (TPSA) indicates drug bioavailability. Oral bioavailability is likely low for substances with a TPSA greater than 140 that are passively absorbed; therefore, all prepared compounds fulfill this condition except for 3a, 3b, 3c, 4b, and 4c. The BOILED-Egg study 2b has high absorption in the gastrointestinal absorption score (GI absorption score), which estimates how well a molecule is absorbed in the small intestine after being taken orally and has excellent pharmacokinetic qualities based on the obtained results. If the result were high, the absorption would be high. The Swiss ADME software has also studied the blood-brain barrier (BBB) permeant. All synthesized compounds have no (BBB), indicating they aren’t BBB- permeant. 2a, 2c, 2d, 2e, 4a, and 5; these derivatives expect to achieve high absorption in the digestive system but aren’t penetrated in the central nervous system (CNS) by p-glycoprotein. This data is illustrated in Tables 2, 3 and Figure 1. Table 2. Predicted ADME properties of the synthesized compounds. Physiochemical properties Medicinal chemistry Drug linkness Pharmacokinetics Comp. NO. M.wta (≤ 500) NO HBDb (≤ 5) NO HBAc (≤ 10) NO RBd TPSAe (Ų) Log Po/w (iLOGP)F (≤ 5) Synthetic accessibility B.Sg P-gph BBB permeanti GI Absj 2a 354.37 4 4 11 116.40 1.80 2.41 0.55 NO NO High 2b 414.42 4 6 13 134.88 2.53 2.67 0.55 YES NO High 2c 423.25 4 4 11 116.40 2.06 2.61 0.55 NO NO High 2d 423.25 4 4 11 116.40 2.64 2.50 0.55 NO NO High 2e 423.25 4 4 11 116.40 2.12 2.49 0.55 NO NO High 3a 426.46 4 8 11 167.30 0.65 3.19 0.55 YES NO Low 3b 584.25 4 8 11 167.30 0.99 3.26 0.55 YES NO Low 3c 454.52 4 8 11 167.30 1.59 3.33 0.55 YES NO Low 4a 326.40 4 4 11 82.26 1.88 2.48 0.55 NO NO High 4b 416.39 4 8 13 173.90 1.64 3.00 0.55 YES NO Low 4c 416.39 4 8 13 173.90 1.03 2.79 0.55 YES NO Low 5 382.42 4 6 13 116.40 2.05 2.79 0.55 NO NO High a Molecular weight, b Number of hydrogen bond donor, c Number of hydrogen bond acceptors, dNumber of rotatable bonds eTopological polar surface area, f logarithm of n-octanol-water partition coefficient, g Bioavailability score, hglyco protein substrate, iBlood–brain barrier, jGI gastrointestinal system. Table 3. Docking scores estimated binding energy (kcal/mol) the binding energies for derivatives and colchicine docked with 1SA0. Comp. number Binding Energy (PLP Fitness) (Kcal/mol) No. of Amino acids included in H-bonding Amino acids included in H-bonding No. of bonding Power of bonding 2a 67.18 2 LYS 254 1 2.857 ASN 101 1 2.923 2b 66.87 1 GLN 247 1 3.029 2c 69.99 1 LYS 254 1 2.616 2d 67.52 2 SER 178 1 2.841 THR 179 1 2.736 2e 66.25 1 LYS 254 1 2.539 IHJPAS. 2025, 38 (1) 322 3a 68.62 2 LYS 254 1 2.812 ASN 101 1 2.760 3c 67.07 2 ASN 101 2 2.914 2.911 TYR 224 1 2.986 4a 67.40 2 ASN 101 1 2.815 GLN 11 1 2.944 4b 69.57 2 GLY 144 1 2.984 LYS 254 1 2.796 4c 65.05 3 TYR 224 1 2.910 LYS 254 1 3.065 THR 179 1 3.023 5 71.77 1 LYS 254 1 2.825 Colchicine 52.44 3 ASN 101 1 2.733 LYS 254 1 2.989 SER 178 1 2.928 Figure 1. Interactions between target protein residues and various ligands: Ligands are shown as ball and stick shapes, with green, blue, red, and yellow representing carbon, nitrogen, oxygen, and sulfur atoms, respectively. Side chain residues are shown as sticks, with gray, blue, and red representing carbon, nitrogen, and oxygen atoms, sequentially. colchicine 2a 2b 2c 2d 2e 3a 3c 4a 4b 4c 5 IHJPAS. 2025, 38 (1) 323 4. Conclusion The purpose of the current study was to prepare a series of different derivatives (1–5) derived from benzoyl chloride, benzyl chloride, sulphonyl chloride, and phenacyl chloride. After that study, molecular docking and ADME were supported by a Boiled Egg study with product yields ranging from 58 to 88%, and all of the prepared derivatives were proved by FT-IR, 1H NMR, and 13 CNMR spectra. Among the prepared compounds, according to molecular docking studies, all synthesized compounds gave excellent results by showing the best bonding into the active site of 1SA0 protein, which candidate it to be good anti-bacterial against Escherichia coli and anti-breast cancer so that all synthesis compounds give excellent results by showing the best bonding (theoretically) in the active site of the 1SA0 protein, compared to colchicine drug. One of the more significant findings to emerge from this study is that the 2b derivative exhibits the most excellent absorption in GI and has a good bonding with the active site of the protein more than the colchicine drug, and derivative 5 has the highest bonding into the active site of 1SA0 protein more than colchicine drug. Still, it can’t penetrate the (CNS). Acknowledgment The authors thank the Department of Chemistry, College of Sciences, University of Baghdad, for providing chemicals and support. 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