Date of Publication
11-7-2025
Document Type
Bachelor's Thesis
Degree Name
Bachelor of Science in Biochemistry
Subject Categories
Chemistry
College
College of Science
Department/Unit
Chemistry
Thesis Advisor
Glenn Kelly U. Tan
Defense Panel Member
Stephani Joy Y. Macalino
Virgilio D. Ebajo Jr.
Abstract (English)
The potential of 6-(4-chlorophenyl)-2-(4-phenol)-5-(1-methyl-5-methylsulfonyl-1H-benzimidazole-2-yl)-imidazo[2,1b][1,3,4]thiadiazole (compound 9), as a to B-cell lymphoma 2 (Bcl-2) inhibitor, was investigated by doing ADME profiling, toxicity prediction, molecular docking, molecular dynamics (MD) simulations, and binding free energy (MM/PBSA) calculations. The precursor compounds: (E/Z)-2-(4-hydroxybenzylidene)hydrazine-1-carbothioamide (Compound 3, 95.58%) and 4-(5-amino-1,3,4-thiadiazole-2-yl)phenol (Compound 4, 0.98%) were also synthesized and characterized through melting point determination and infrared spectroscopy. ADME results indicated that compound 9 satisfied major drug-likeness rules with favorable solubility, gastrointestinal absorption, and oral bioavailability. Toxicity predictions across ProTox-3, ADMETlab3, and DeepPK revealed a safer profile than venetoclax, chosen as the positive control of the study as it is a highly selective FDA-approved Bcl-2 inhibitor, particularly in immunotoxicity, cardiotoxicity, and mutagenicity. Docking studies showed a strong binding affinity of compound 9 (-9.2148 kcal/mol), highlighting strong and stable interactions with the Bcl-2 BH3 binding groove. MD simulations confirmed complex stability, with RMSD values below 0.4 nm and favorable interaction profiles with multiple polar and hydrophobic interactions. MM/PBSA analyses further validated the binding energetics, with conformation (1) exhibiting the most favorable interaction energy of 54.43 ± 4.15 kcal/mol. Overall, results demonstrate that compound 9 possesses promising physicochemical, pharmacokinetic, and dynamic stability characteristics, supporting its potential as a molecule for Bcl-2-targeted anticancer therapy in hematologic malignancies, such as leukemia, and some solid tumor cancers including breast cancer.
Abstract Format
html
Abstract (Filipino)
Sinuri ang potensyal ng 6-(4-chlorophenyl)-2-(4-phenol)-5-(1-methyl-5-methylsulfonyl-1H-benzimidazole-2-yl)-imidazo[2,1-b][1,3,4]thiadiazole (compound 9) bilang inhibitor ng B-cell lymphoma 2 (Bcl-2) sa pamamagitan ng pag-aaral ng ADME profiling, prediksiyon ng toksisidad, molecular docking, molecular dynamics (MD) simulations, at pagkalkula ng binding free energy (MM/PBSA). Ang mga precursor na compound: (E/Z)-2-(4-hydroxybenzylidene)hydrazine-1-carbothioamide (Compound 3, 95.58%) at 4-(5-amino-1,3,4-thiadiazole-2-yl)phenol (Compound 4, 0.98%) ay isinynthesize at kinilala gamit ang pagtukoy ng melting point at infrared spectroscopy. Ipinakita ng mga resulta ng ADME na ang compound 9 ay pumasa sa mga pangunahing patakaran sa drug-likeness na may kanais-nais na solubility, gastrointestinal absorption, at oral bioavailability. Ang mga prediksiyon ng toksisidad mula sa ProTox-3, ADMETlab3, at DeepPK ay nagpakita ng mas ligtas na profile kumpara sa venetoclax, na ginamit bilang positibong kontrol bilang isang FDA-approved at highly selective na Bcl-2 inhibitor, partikular sa immunotoxicity, cardiotoxicity, at mutagenicity. Ipinakita ng molecular docking ang malakas na binding affinity ng compound 9 (-9.2148 kcal/mol), na nagha-highlight ng matatag na interaksiyon sa Bcl-2 BH3 binding groove. Kinumpirma ng MD simulations ang katatagan ng complex, na may RMSD values na mas mababa sa 0.4 nm at kanais-nais na mga profile ng interaksiyon na binubuo ng maraming polar at hydrophobic interactions. Pinagtibay pa ng MM/PBSA analysis ang binding energetics, kung saan ang conformation (1) ay nagpakita ng pinaka-paborableng interaction energy na 54.43 ± 4.15 kcal/mol. Sa kabuuan, ipinapakita ng mga resulta na ang compound 9 ay nagtataglay ng mahuhusay na physicochemical, pharmacokinetic, at dynamic stability characteristics, na sumusuporta sa potensyal nito bilang molekulang maaaring gamitin sa Bcl-2-targeted anticancer therapy para sa mga hematologic malignancies gaya ng leukemia, at ilang solid tumor cancers kabilang ang breast cancer.
Abstract Format
html
Language
English
Format
Electronic
Keywords
Antineoplastic antibiotics; Benzimidazoles
Recommended Citation
Pabilonia, J. C., & Pascasio, M. S. (2025). Precursor synthesis and in silico evaluation of 6-(4-chlorophenyl)-2-(4-phenol)-5-(1-methyl-5-methylsulfonyl-1H-benzimidazole-2-yl)-imidazo[2,1-b][1,3,4]thiadiazole as a potential Bcl-2 inhibitor. Retrieved from https://animorepository.dlsu.edu.ph/etdb_chem/75
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Embargo Period
12-2-2026
