In silico study of new carbonic anhydrase inhibitor derivatives bearing 1, 3, 4-Oxadiazole moiety with promising anti-cancer activity.


  • Riyam Saad Aljubouri Department of pharmaceutical chemistry, college of Pharmacy, University of Kufa, Najaf, Iraq
  • Noor H. Naser Department of pharmaceutical chemistry, college of Pharmacy, Al-Zhraa University for women, Karbala, Iraq



cancer, chemotherapy, in silico, oxadiazole moiety, sulfanilamide derivatives, carbonic anhydrase.


Objectives: Molecular docking simulations were performed to assess the theoretical binding affinities of six (6) compounds created where they are derivatives having 1,3,4, oxadiazole moiety, and their target was cancer and Human carbonic anhydrase IX (PDB code: 6U4T). Using ChemDraw Ultra 12.0, the molecular structure was meticulously sketched. Molecular Operating environment software was used to verify the developed compounds by looking at their S. score and Rmsd values. Promising activity was seen with these proteins from the theoretically generated compounds, which exhibited strong binding contacts with the receptor active pocket.


Methods: Chemically by joining together several oxadiazole derivatives, sulfanilamide analogues (IVa-IVd) may be created in the lab. Molecular docking and ligand/receptor priming by MOE software.

Results: Acetazolamide was selected because it had the same pharmacophore as the sulfanilamide group, and cisplatin was used in clinical trials for cancer therapy. IVc and IVa yielded max score and irrevocable relationship compared with acetazolamide and cisplatin.

Conclusion: The MOE docking results validated the potent anticancer activity, the identified compounds showing good binding affinity with target proteins relative to the reference drugs (Acetazolamide and cisplatin). The most effective anticancer compounds were IVc and IVa, which yielded a maximum score with a Rmsd of less than 2, the MOE docking results were able prove this.

Compounds IVc and IVa exhibited the greatest cytotoxic impact of the synthetic compounds against MCF7, and all four synthesized compounds showed a superior safety profile than the standards in MCF10a.


Y. Teng, X. Xie, S. Walker, D. T. White, J. S. Mumm, and J. K. Cowell, “Evaluating

human cancer cell metastasis in zebrafish,” BMC Cancer, vol. 13, no. 1, pp.

–12, 2013.

R. L. Siegel, K. D. Miller, and A. Jemal, “Ca A Cancer Journal for Clinicians

Cancer statistics,” Cancer Statistics, vol. 56, no. 2, p. 106, 2015.

N. G. Zaorsky et al., “Causes of death among cancer patients,” Annals of

Oncology, vol. 28, no. 2, pp. 400–407, 2017.

El-Husseiny, W. M., Magda, A. A., Abdel-Aziz, N. I., El-Azab, A. S., Asiri, Y. A.,

& Alaa, A. M. (2018). Structural alterations based on naproxen scaffold:

Synthesis, evaluation of antitumor activity and COX-2 inhibition, and

molecular docking. European Journal of Medicinal Chemistry, 158, 134–143.

T. N. Seyfried and L. C. Huysentruyt, “On the origin of cancer metastasis,” Crit

Rev Oncog, vol. 18, no. 1–2, 2013.

Dysphagia Section, Oral Care Study Group, Multinational Association of

Supportive Care in Cancer (MASCC)/International Society of Oral Oncology

(ISOO), Raber-Durlacher, J. E., Brennan, M. T., Verdonck-de Leeuw, I. M.,

Gibson, R. J., Eilers, J. G., ... & Spijkervet, F. K. (2012). Swallowing dysfunction

in cancer patients. Supportive Care in Cancer, 20, 433–443.

C. Shao et al., “Role of hypoxia-induced exosomes in tumor biology,” Mol

Cancer, vol. 17, no. 1, pp. 1–8, 2018, doi: 10.1186/s12943-018-0869-y.

K. Wang, B. Yu, and J. L. Pathak, “An update in clinical utilization of

photodynamic therapy for lung cancer,” J Cancer, vol. 12, no. 4, p. 1154, 2021.

L. Gatti and F. Zunino, “Overview of tumor cell chemoresistance

mechanisms.,” Methods Mol Med, vol. 111, pp. 127–148, 2005, doi:


S. Pastorekova, P. J. Ratcliffe, and J. Pastorek, “Molecular mechanisms of

carbonic anhydrase IX‐mediated pH regulation under hypoxia,” BJU Int, vol.

, pp. 8–15, 2008.

S. C. Frost, “Physiological functions of the alpha class of carbonic

anhydrases,” Carbonic anhydrase: mechanism, regulation, links to disease,

and industrial applications, pp. 9–30, 2014.

M.-C. Hsin, Y.-H. Hsieh, Y.-H. Hsiao, P.-N. Chen, P.-H. Wang, and S.-F. Yang,

“Carbonic anhydrase IX promotes human cervical cancer cell motility by

regulating PFKFB4 expression,” Cancers (Basel), vol. 13, no. 5,

p. 1174, 2021.

S. Pastorekova, M. Zatovicova, and J. Pastorek, “Cancer-associated carbonic

anhydrases and their inhibition,” Curr Pharm Des, vol. 14, no. 7, pp. 685–698,

D. C. Venugopal et al., “Integrated Proteomics Based on 2D Gel

Electrophoresis and Mass Spectrometry with Validations: Identification of a

Biomarker Compendium for Oral Submucous Fibrosis—An Indian Study,”

J Pers Med, vol. 12, no. 2, p. 208, 2022.

Z. H. Chohan, A. U. Shaikh, A. Rauf, and C. T. Supuran, “Antibacterial,

antifungal and cytotoxic properties of novel N-substituted sulfonamides

from 4-hydroxycoumarin,” J Enzyme Inhib Med Chem, vol. 21, no. 6, pp.

–748, 2006.

U. K. Mondal et al., “PEG linker length strongly affects tumor cell killing by

PEGylated carbonic anhydrase inhibitors in hypoxic carcinomas expressing

carbonic anhydrase IX,” Int J Mol Sci, vol. 22, no. 3, p. 1120, 2021.

A. Janoniene and V. Petrikaite, “In search of advanced tumor diagnostics

and treatment: Achievements and perspectives of Carbonic Anhydrase IX

targeted delivery,” Mol Pharm, vol. 17, no. 6, pp. 1800–1815, 2020.

C. T. Supuran, “Special Issue: Sulfonamides,” Molecules, vol. 22, no. 10, 2017,

doi: 10.3390/molecules22101642.

O. M. Hendawy, “A comprehensive review of recent advances in the

biological activities of 1, 2, 4‐oxadiazoles,” Arch Pharm (Weinheim), vol. 355,

no. 7, p. 2200045, 2022.

R. M. M. El-Hazek, N. H. Zaher, H. E. S. Emam, M. G. El-Gazzar, and A. Khalil,

“Pyrazole-sulfonamide scaffold featuring dual-tail strategy as apoptosis

inducers in colon cancer,” Sci Rep, vol. 13, no. 1, p. 5782, 2023.

T. C. Denner, N. Heise, J. Zacharias, O. Kraft, S. Hoenke, and R. Csuk, “Small

Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity

of Cytotoxic Triterpene Acetazolamide Conjugates,” Molecules, vol. 28, no. 3,

p. 1009, 2023.

J.-J. Wang, W. Sun, W.-D. Jia, M. Bian, and L.-J. Yu, “Research progress on

the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole

derivatives: a mini review.,” J Enzyme Inhib Med Chem, vol. 37, no. 1, pp.

–2319, Dec. 2022, doi: 10.1080/14756366.2022.2115036.

M. J. Ahsan et al., “Rationale Design, Synthesis, Cytotoxicity Evaluation,

and Molecular Docking Studies of 1,3,4-oxadiazole Analogues,” Anticancer

Agents Med Chem, vol. 18, no. 1, pp. 121–138, 2017, doi: 10.2174/18715206

U. A. Atmaram and S. M. Roopan, “Biological activity of oxadiazole and

thiadiazole derivatives.,” Appl Microbiol Biotechnol, vol. 106, no. 9–10,

pp. 3489–3505, May 2022, doi: 10.1007/s00253-022-11969-0.

M. R. Sheehan, A. M. R. Raauf, and N. H. Naser, “In Silico Study and In Vitro

Evaluation of Novel Synthesized Quinolone Derivatives Having Five-

Membered Heterocyclic Moieties,” Egypt J Chem, vol. 65, no. 3,

pp. 215–225, 2022, doi: 10.21608/ejchem.2021.92699.4390.

A. R. Saeed, N. H. Naser, and A. A. A. Alard, “Design, Synthesis and

Pharmacological Evaluation of New Lomefloxacin Derivatives Having

Oxadiazole Nucleus,” Journal of Pharmaceutical Sciences and Research,

vol. 11, no. 4, pp. 1516–1526, 2019.

M. H. Mohammed, M. F. Mahdi, N. H. Naser, and S. M. Ali, “Design, synthesis

and pharmacological evaluation of sulfanilamide-ciprofloxacin conjugates

utilizing hybridization approach as new antibacterial agents,” J Nat Sci Res,

vol. 15, no. 4, p. 106, 2015.

M. H. M. Noor Hatef Aldabagh, “Design, and synthesis of Novel Antituberculosis

Agents,” Scholar’s Press, p. 69, 2017.

A. Tripathi and K. Misra, “Molecular docking: A structure-based drug

designing approach,” JSM Chem, vol. 5, no. 2, pp. 1042–1047, 2017.




How to Cite

Saad Aljubouri, R. ., & H. Naser, N. . (2023). In silico study of new carbonic anhydrase inhibitor derivatives bearing 1, 3, 4-Oxadiazole moiety with promising anti-cancer activity. Journal of Contemporary Medical Sciences, 9(5).