Assessing β-carboline analogues as antibiotic agent using in vitro studies
List of Authors
  • Nur Anis Afiqah Jasmin

Keyword
  • Antibacterial, Bacterial, Β-Carboline, In Vitro

Abstract
  • The mortality rate caused by bacterial diseases and bacterial antimicrobial resistance (AMR) is a significant concern in global public health. There is an urgent demand for new therapeutic agents that not only offer improved efficiency but also entail fewer secondary effects, addressing the challenges posed by the currently available drugs used in clinical practice. In this study, 40 analogues of β-carboline were subjected to solubility tests to determine their solubility. Among them, 22 analogues proved to be soluble and were subsequently tested for in vitro antibacterial activity using the agar disc diffusion method against S. aureus and E. coli to evaluate their effectiveness. The results of the in vitro antibacterial studies revealed that compounds 1h, 7d, and 1l displayed appreciable growth-inhibitory effects against E. coli, while compounds 1a, 1f, 1l, and 1j exhibited appreciable growth-inhibitory effects against S. aureus. Notably, compounds 1j and 1l displayed the highest growth-inhibitory potency against S. aureus and E. coli, respectively, out of the 22 compounds tested. Of all the analogues examined, 1l and 1j demonstrated the most substantial growth-inhibitory effects against E. coli and S. aureus, respectively, underscoring their potential as inhibitors.

Reference
  • 1. Abushaheen, M. A., Muzaheed, Fatani, A. J., Alosaimi, M., Mansy, W., George, M., Acharya, S., Rathod, S., Divakar, D. D., Jhugroo, C., Vellappally, S., Khan, A. A., Shaik, J., & Jhugroo, P. (2020). Antimicrobial resistance, mechanisms and its clinical significance. Disease-a-Month, 66(6). https://doi.org/10.1016/j.disamonth.2020.100971.

    2. Aryal, B., Raut, B. K., Bhattarai, S., Bhandari, S., Tandan, P., Gyawali, K., Sharma, K., Ranabhat, D., Thapa, R., Aryal, D., Ojha, A., Devkota, H. P., & Parajuli, N. (2022). Potential Therapeutic Applications of Plant-Derived Alkaloids against Inflammatory and Neurodegenerative Diseases. Evidence-Based Complementary and Alternative Medicine, 2022. https://doi.org/10.1155/2022/7299778.

    3. Ash’ari, N. A. N., Pungot, N. H., Shaameri, Z., & Jani, N. A. (2021). A facile synthesis of n-alkylated daibucarboline a derivatives via pictet-spengler condensation of tryptamine. Malaysian Journal of Analytical Sciences, 25(5), 706–715.

    4. Aslam, B., Wang, W., Arshad, M. I., Khurshid, M., Muzammil, S., Rasool, M. H., Nisar, M. A., Alvi, R. F., Aslam, M. A., Qamar, M. U., Salamat, M., & Baloch, Z. (2018). Antibiotic resistance: a rundown of a global crisis. Infection and drug resistance, 11, 1645–1658. https://doi.org/10.2147/IDR.S173867.

    5. Barakat, K. (2017). Solubility: A Speed-Breaker on the Drug Discovery Highway. MOJ Bioequivalence & Bioavailability, 3(3), 56–58. https://doi.org/10.15406/mojbb.2017.03.00033.

    6. Calvo-Flores, F. G., Monteagudo-Arrebola, M. J., Dobado, J. A., & Isac-García, J. (2018). Green and Bio-Based Solvents. Topics in current chemistry (Cham), 376(3), 18. https://doi.org/10.1007/s41061-018-0191-6.

    7. Chanda-Kapata, P., Kapata, N., & Zumla, A. (2020). COVID-19 and malaria: A symptom screening challenge for malaria endemic countries. International Journal of Infectious Diseases, 94, 151-153. https://doi.org/10.1016/j.inid.2020.04.007.

    8. Church, N. A., & McKillip, J. L. (2021). Antibiotic resistance crisis: challenges and imperatives. Biologia, 76(5), 1535–1550. https://doi.org/10.1007/s11756-021-00697-x.

    9. CLSI. (2020). Standards for antimicrobial susceptibility testing. American Journal of Veterinary Research, 40, 18–30.

    10. Dass, S. A., Balakrishnan, V., Arifin, N., Lim, C. S. Y., Nordin, F., & Tye, G. J. (2022). The COVID-19/Tuberculosis Syndemic and Potential Antibody Therapy for TB Based on the Lessons Learnt From the Pandemic. Frontiers in immunology, 13, 833715. https://doi.org/10.3389/fimmu.2022.833715.

    11. Dhingra, S., Rahman, N. A. A., Peile, E., Rahman, M., Sartelli, M., Hassali, M. A., Islam, T., Islam, S., & Haque, M. (2020). Microbial Resistance Movements: An Overview of Global Public Health Threats Posed by Antimicrobial Resistance, and How Best to Counter. Frontiers in public health, 8, 535668. https://doi.org/10.3389/fpubh.2020.535668.

    12. Fletcher S. (2015). Understanding the contribution of environmental factors in the spread of antimicrobial resistance. Environmental health and preventive medicine, 20(4), 243–252. https://doi.org/10.1007/s12199-015-0468-0.

    13. Huizen, J. (2020, August 29). Bacterial infection symptoms: Signs and treatment. Medical News Today. https://www.medicalnewstoday.com/articles/bacterial-infection-symptoms

    14. Kelly, D. F., Thorson, S., Maskey, M., Mahat, S., Shrestha, U., Hamaluba, M., Williams, E., Dongol, S., Werno, A. M., Portess, H., Yadav, B. K., Adhikari, N., Guiver, M., Thomas, K., Murdoch, D. R., & Pollard, A. J. (2011). The burden of vaccine-preventable invasive bacterial infections and pneumonia in children admitted to hospital in urban Nepal. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 15(1), e17–e23. https://doi.org/10.1016/j.ijid.2010.05.021.

    15. Kerns, E. H., Di, L., & Carter, G. T. (2008). In vitro solubility assays in drug discovery. Current drug metabolism, 9(9), 879–885. https://doi.org/10.2174/138920008786485100.

    16. Langford, B. J., So, M., Raybardhan, S., Leung, V., Westwood, D., MacFadden, D. R., Soucy, J. P. R., & Daneman, N. (2020). Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. In Clinical Microbiology and Infection (Vol. 26, Issue 12, pp. 1622-1629). Elsevier B.V. https://doi.org/10.1016/j.cmi.2020.07.016.

    17. Langford, B. J., So, M., Raybardhan, S., Leung, V., Soucy, J. P. R., Westwood, D., Daneman, N., & MacFadden, D. R. (2021). Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis. In Clinical Microbiology and Infection (Vol. 27, Issue 4, pp. 520-531). Elsevier B. V. https://doi.org/10.1016/j.cmi.2020.12.018

    18. Liu, H., Taylor, T. H., Jr, Pettus, K., Johnson, S., Papp, J. R., & Trees, D. (2016). Comparing the disk-diffusion and agar dilution tests for Neisseria gonorrhoeae antimicrobial susceptibility testing. Antimicrobial resistance and infection control, 5, 46. https://doi.org/10.1186/s13756-016-0148-x.

    19. Magiorakos, A. P., Srinivasan, A., Carey, R. B., Carmeli, Y., Falagas, M. E., Giske, C. G., Harbarth, S., Hindler, J. F., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D. L., Rice, L. B., Stelling, J., Struelens, M. J., Vatopoulos, A., Weber, J. T., & Monnet, D. L. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 18(3), 268–281. https://doi.org/10.1111/j.1469-0691.2011.03570.x.

    20. Manyi-Loh, C., Mamphweli, S., Meyer, E., & Okoh, A. (2018). Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications. Molecules (Basel, Switzerland), 23(4), 795. https://doi.org/10.3390/molecules23040795.

    21. Ordi, J., Castillo, P., Garcia-Basteiro, A. L., Moraleda, C., Fernandes, F., Quintó, L., Hurtado, J. C., Letang, E., Lovane, L., Jordao, D., Navarro, M., Bene, R., Nhampossa, T., Ismail, M. R., Lorenzoni, C., Guisseve, A., Rakislova, N., Varo, R., Marimon, L., Sanz, A., Menéndez, C. (2019). Clinico-pathological discrepancies in the diagnosis of causes of death in adults in Mozambique: A retrospective observational study. PloS one, 14(9), e0220657. https://doi.org/10.1371/journal.pone.0220657.

    22. Quan, H., Li, B., Couris, C. M., Fushimi, K., Graham, P., Hider, P., Januel, J. M., & Sundararajan, V. (2011). Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. American journal of epidemiology, 173(6), 676–682. https://doi.org/10.1093/aje/kwq433.

    23. Quashie, N. B., & Duah-Quashie, N. O. (2021). Treatment of COVID-19 with Chloroquine: Implication for Malaria Chemotherapy Using ACTs in Disease Endemic Countries. Journal of tropical pediatrics, 67(1), fmaa089. https://doi.org/10.1093/tropej/fmaa089.

    24. Raimondi, M. V., Randazzo, O., La Franca, M., Barone, G., Vignoni, E., Rossi, D., & Collina, S. (2019). DHFR Inhibitors: Reading the Past for Discovering Novel Anticancer Agents. Molecules (Basel, Switzerland), 24(6), 1140. https://doi.org/10.3390/molecules24061140..

    25. Ramesh, C., & Pattar, M. G. (2010). Antimicrobial properties, antioxidant activity and bioactive compounds from six wild edible mushrooms of western ghats of Karnataka, India. Pharmacognosy Research, 2(2), 107. https://doi.org/10.4103/0974-8490.62953.

    26. Rossiter, S. E., Fletcher, M. H., & Wuest, W. M. (2017). Natural Products as Platforms To Overcome Antibiotic Resistance. Chemical reviews, 117(19), 12415–12474. https://doi.org/10.1021/acs.chemrev.7b00283.

    27. Sengupta, S., Chattopadhyay, M. K., & Grossart, H. P. (2013). The multifaceted roles of antibiotics and antibiotic resistance in nature. Frontiers in microbiology, 4, 47. https://doi.org/10.3389/fmicb.2013.00047

    28. Sourkes, T.L. 1999. “Rational hope” in the early treatment of Parkinson’s disease. Can. J. Physiol. Pharm 77(6):375–382.

    29. Spellberg, B., Srinivasan, A., & Chambers, H. F. (2016). New Societal Approaches to Empowering Antibiotic Stewardship. JAMA, 315(12), 1229–1230. https://doi.org/10.1001/jama.2016.1346

    30. Subedi, N., Bhattarai, S., Ranabhat, S., Sharma, B. K., Baral, M. P., & Upadhyaya, T. L. (2021). Disseminated cryptococcosis in a deceased with HIV-1 diagnosed by minimally invasive tissue sampling technique. Clinical case reports, 9(3), 1667–1671. https://doi.org/10.1002/ccr3.3865.

    31. Szabó, T., Volk, B., & Milen, M. (2021). Recent Advances in the Synthesis of β-Carboline Alkaloids. Molecules (Basel, Switzerland), 26(3), 663. https://doi.org/10.3390/molecules26030663.

    32. Ventola C. L. (2015). The antibiotic resistance crisis: part 1: causes and threats. P & T : a peer-reviewed journal for formulary management, 40(4), 277–283. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4378521/.

    33. Williams, E. J., Thorson, S., Maskey, M., Mahat, S., Hamaluba, M., Dongol, S., Werno, A. M., Yadav, B. K., Shah, A. S., Kelly, D. F., Adhikari, N., Pollard, A. J., & Murdoch, D. R. (2009). Hospital-based surveillance of invasive pneumococcal disease among young children in urban Nepal. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 48 Suppl 2, S114–S122. https://doi.org/10.1086/596488.