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Bazı Yeni Pirol Türevlerinin Klopman İndeks Tanımlayıcı Kullanarak 4D-QSAR Analizi

Yıl 2022, Cilt: 15 Sayı: 1, 168 - 182, 27.03.2022
https://doi.org/10.18185/erzifbed.973326

Öz

Öz
Ligand-Reseptör (L-R) arasındaki 3 Boyutlu (3-Dimensional,3D) etkileşimler için yeni olarak kullanmaya başladığımız Yerel Reaktif Tanımlayıcı (Local Reactive Descriptor, LRD) olan Klopman İndeksi’ni antitüberküloz ajanlar olarak bazı yeni pirol türevlerinde 4D-QSAR incelemeleri için uyguladık. L-R arasında ileri sürülen etkileşim noktalarından oluşan farmakofora (Pharmacophore, Pha) ait reseptör tarafının parametreleri, ligand tarafındaki LRD değerlerine bağlı olarak geliştirdiğimiz MCET yönteminde hesaplandı. Eğitim setindeki moleküller üzerinde Leave One Out Cross-Validation (LOO-CV) tekniği ile 4D-QSAR modeli kurulduktan sonra harici test setindeki moleküller üzerinde model doğrulandı. Her iki setten elde edilen istatistik sonuçları, sırasıyla, Q2=0.875 ve Rext2=0.918 değerleri tatmin edici olarak değerlendirildi.

Kaynakça

  • Referans1 Ahmadi, A., Solati, J., Hajikhani, R., Pakzad, S. 2011. “Synthesis and Analgesic Effects of New pyrrole derivatives of phencyclidine in mice”, Arzneimittelforsch, 61, 296-300.
  • Referans2 Alp Tokat, T., Turkmenoglu, B., Guzel, Y., Kizilcan, D. S. 2019. “Investigation of 3D Pharmacophore Of N-benzyl Benzamide Molecules of Melanogenesis Inhibitors Using a New Descriptor Klopman Index: Uncertainties in Model”, J Mol Model, 25(8), 247.
  • Referans3 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y. 1987. “The Electron-Topological Approach in Investigation of Structure - Activity Relation - Inhibition of Thymidine Phosphorylase by Uracil Derivatives”, Bioorg Khim+, 13, 38-44.
  • Referans4 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y., Greni, A. I., Vysotskaya, L. E., Mikhailova, T. V. 1989 “Study Of The Electronic And Structural-Properties Of The Chemical-Compounds İn Garlic Aroma”, Nahrung, 33, 405-411.
  • Referans5 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y., Vlad, P. F. 1991. “Origin of Musk Fragrance Activity - the Electron-Topologic Approach”, New J Chem, 15, 307-320.
  • Referans6Biava, M., Porretta, G. C., Poce, G., Battilocchio, C., Alfonso, S., De Logu, A., Serra, N., Manetti, F., Botta, M. 2010. “Identification Of A Novel Pyrrole Derivative Endowed With Antimycobacterial Activity And Protection Index Comparable To That Of The Current Antitubercular Drugs Streptomycin And Rifampin”, Bioorg Med Chem, 18, 8076-8084.
  • Referans7 Consonni, V., Todeschini, R. 2010. “Molecular Descriptors”, Chall Adv Comput Che, 8, 29-102.
  • Referans8 Cramer, R. D., Patterson, D. E., Bunce, J. D. 1988. “Comparative Molecular-Field Analysis (Comfa) .1. Effect of Shape on Binding of Steroids to Carrier Proteins”, J Am Chem Soc, 110, 5959-5967.
  • Referans9 Dimoglo, A. S., Beda, A. A., Shvets, N. M., Gorbachov, M. Y., Kheifits, L. A., Aulchenko, I. S. 1995. “Investigation of the Relationship between Sandalwood Odor and Chemical-Structure - Electron-Topological Approach”, New J Chem, 19, 149-154.
  • Referans10 Dimoglo, A. S., Bersuker, I. B., Popa, D. P., Kuchkova, K. I. 1989. “The Electron-Topological Study of the Growth-Regulating Activity in a Series of Abscisic-Acid Analogs”, Teor Eksp Khim, 25, 590-594.
  • Referans11 Duncan, K., Barry, C. E. 2004. “Prospects For New Antitubercular Drugs”, Curr Opin Microbiol, 7, 460-465.
  • Referans12 Guzel, Y., Aslan, E., Turkmenoglu, B., Su, E. M. 2018. “4D-QSAR Studies Using a New Descriptor of the Klopman Index: Antibacterial Activities of Sulfone Derivatives Containing 1, 3, 4-Oxadiazole Moiety Based on MCET Model”, Curr Comput-Aid Drug, 14, 207-220.
  • Referans13 Hong, X., Hopfinger, A. J. 2003. “3D-Pharmacophores of Flavonoid Binding at the Benzodiazepine GABA (A) Receptor Site Using 4D-QSAR Analysis”, J Chem Inf Comp Sci, 43, 324-336.
  • Referans14 https://www.who.int/campaigns/world-tb-day/world-tb-day-2019, in.
  • Referans15 Joshi, S. D., More, U. A., Dixit, S. R., Korat, H. H., Aminabhavi, T. M., Badiger, A. M. 2014. “Synthesis, Characterization, Biological Activity, and 3D-QSAR Studies on Some Novel Class of Pyrrole Derivatives as Antitubercular Agents”, Med Chem Res, 23, 1123-1147.
  • Referans16 Kamal, A., Ramakrishna, G., Nayak, V. L., Raju, P., Rao, A. V. S., Viswanath, A., Vishnuvardhan, M. V. P. S., Ramakrishna, S., Srinivas, G. 2012. “Design and Synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine Conjugates as Potential Anticancer Agents”, Bioorgan Med Chem, 20, 789-800.
  • Referans17 Kizilcan, D. S., Turkmenoglu, B., Guzel, Y. 2020. “The Use of the Klopman İndex as A New Descriptor for Pharmacophore Analysis on Strong Aromatase İnhibitor Flavonoids against Estrogen-Dependent Breast Cancer”, Struct Chem, 31, 1339-1351.
  • Referans18 Klebe, G., Abraham, U., Mietzner, T. 1994. “Molecular Similarity Indexes in a Comparative-Analysis (Comsia) of Drug Molecules to Correlate and Predict Their Biological-Activity”, J Med Chem, 37, 4130-4146.
  • Referans19 Klopman, G. (1968). Chemical reactivity and the concept of charge- and frontier-controlled reactions. Journal of the American Chemical Society, 90(2), 223-234.
  • Referans20 Klopman, G. (1984a). Citation Classic - Chemical-Reactivity and the Concept of Charge-Controlled and Frontier-Controlled Reactions. Current Contents/Engineering Technology & Applied Sciences(20), 16-16. Retrieved from <Go to ISI>://WOS:A1984SP75100001
  • Referans21 Klopman, G. (1984b). Citation Classic - Chemical-Reactivity and the Concept of Charge-Controlled and Frontier-Controlled Reactions. Current Contents/Physical Chemical & Earth Sciences(20), 16-16. Retrieved from <Go to ISI>://WOS:A1984SP74700001
  • Referans22 Kubinyi, H. 1988. “Free Wilson Analysis - Theory, Applications and Its Relationship to Hansch Analysis”, Quant Struct-Act Rel, 7, 121-133.
  • Referans23 Leszczynskı, J. (2010), “Recent Advances in QSAR Studies: Methods and Applications, Chall Adv Comput Che, 8”, Springer Science+Business Media, Springer Dordrecht Heidelberg London New York, 1-423.
  • Referans24 LoPachin, R. M., Gavin, T. 2016. “Reactions Of Electrophiles With Nucleophilic Thiolate Sites: Relevance to Pathophysiological Mechanisms and Remediation”, Free Radical Res, 50, 195-205.
  • Referans25 Mohamed, M. S., Kamel, R., Fathallah, S. S. 2011. “Synthesis of New Pyrroles of Potential Anti-Inflammatory Activity”, Arch Pharm, 344, 830-839.
  • Referans26 Nantasenamat, C., Isarankura-Na-Ayudhya, C., Naenna, T., Prachayasittikul, V. 2009. “A Practical Overview of Quantitative Structure-Activity Relationship”, Excli J, 8, 74-88.
  • 27. Referans27 Nantasenamat, C., Isarankura-Na-Ayudhya, C., Prachayasittikul, V. 2010. “Advances in computational methods to predict the biological activity of compounds”, Expert Opin Drug Dis, 5 (2010) 633-654.
  • Referans28 Ragno, R., Marshall, G. R., Di Santo, R., Costi, R., Massa, S., Rompei, R., Artico, M. 2000. “Antimycobacterial Pyrroles: Synthesis, Anti-Mycobacterium Tuberculosis Activity and QSAR Studies”, Bioorgan Med Chem, 8, 1423-1432.
  • Referans29 Randic, M. 1996. “Molecular bonding profiles”, J Math Chem, 19, 375-392.
  • Referans30 Salem, L. 1968. “Intermolecular Orbital Theory of the İnteraction between Conjugated Systems. I. General Theory”, J Am Chem Soc, 90, 543-552.
  • Referans31 Saripinar, E., Guzel, Y., Patat, S., Yildirim, I., Akcamur, Y., Dimoglo, A. S. 1996. “Electron-Topological Investigation of the Structure-Antitubercular Activity Relationship of Thiosemicarbazone Derivatives”, Arzneimittel-Forschung/Drug Research, 46, 824-828.
  • Referans32 Sbardella, G., Mai, A., Artico, M., Loddo, R., Setzu, M. G., La Colla, P. 2004. “Synthesis and in Vitro Antimycobacterial Activity of Novel 3-(1H-pyrrol-1-yl)-2-oxazolidinone Analogues of PNU-100480”, Bioorg Med Chem Lett, 14, 1537-1541.
  • Referans33 Sippl, W, 2010. “3D-QSAR-Applications, Recent Advances, and Limitations”, Chall Adv Comput Che, 8, (ed., Puzyn, T., Leszczynski, J., Cronin, M. T. D.), Springer Science+Business Media, Springer Dordrecht Heidelberg London New York, 103-125.
  • Referans34 Türkmenoğlu, B., and Güzel, Y. 2021. “Confirmation by molecular docking of the pharmacophore defined as 4D-QSAR using the MCET method for the 2-hydroxydiarylamide derivatives”, International Journal of Chemistry and Technology, 5(1), 11-25.
  • Referans35 Türkmenoğlu, B., and Güzel, Y. 2021. “Klopman Index: A New Descriptor Used In MCET For 3D/4D-QSAR Modeling”, Current Academic Studies in Science and Mathematics Sciences, Livre de Lyon, Lyon, 1-16.
  • Referans36 Turkmenoglu, B., Guzel, Y. 2018. “Molecular Docking And 4D-QSAR Studies of Metastatic Cancer Inhibitor Thiazoles”, Comput Biol Chem, 76, 327-337. Referans37 Turkmenoglu, B., Guzel, Y., Su, E. M., Kizilcan, D. S. 2020. “Investigation Of İnhibitory Activity Of Monoamine Oxidase A With 4D-QSAR Using Fukui İndices İdentifier”, Mater Today Commun, 25, 1-6.
  • Referans38 Türkmenoglu, B., Yilmaz, H., Su, E. M., Alp Tokat, T., Güzel, Y. 2017. “4D-QSAR Study of Flavonoid Derivatives With MCET Method, International Journal of Chemistry and Technology, 1, 14-23.
  • Referans39 Yilmaz, H., Boz, M., Turkmenoglu, B., Guzel, Y. 2014. “Pharmacophore and Functional Group Identification of 4, 4’-dihydroxydiphenylmethane as Bisphenol-A (BSA) Derivative”, Trop J Pharm Res, 13, 117-126.
  • Referans40 Yilmaz, H., Guzel, Y., Onal, Z., Altiparmak, G., Kocakaya, S. O. 2011. “4D-QSAR Study of p56 (lck) Protein Tyrosine Kinase Inhibitory Activity of Flavonoid Derivatives Using MCET Method”, B Korean Chem Soc, 32, 4352-4360.

4D-QSAR Analysis of Some New Pyrrole Derivatives Using Klopman Index Descriptor

Yıl 2022, Cilt: 15 Sayı: 1, 168 - 182, 27.03.2022
https://doi.org/10.18185/erzifbed.973326

Öz

We applied the Klopman Index, the Local Reactive Descriptor (LRD), for 3-Dimensional (3D) interactions between the Ligand-Receptor (L-R), for some new pyrrole derivatives as antituberculosis agents for 4-Dimensional Quantitative Structure-Activity Relationship (4D-QSAR) investigations. The parameters of the receptor side belonging to the Pharmacophore (Pha), which consists of the interaction points suggested between L-R, were calculated in the Molecular Conformer Electron Topological (MCET) method we developed based on the LRD values on the ligand side. After the 4D-QSAR model was established with the Leave One Out Cross-Validation (LOO-CV) technique on the molecules in the training set, the model was confirmed on the molecules in the external test set. Statistical results obtained from both sets, Q2 = 0.875 and Rext2 = 0.918, respectively, were evaluated as satisfactory.

Kaynakça

  • Referans1 Ahmadi, A., Solati, J., Hajikhani, R., Pakzad, S. 2011. “Synthesis and Analgesic Effects of New pyrrole derivatives of phencyclidine in mice”, Arzneimittelforsch, 61, 296-300.
  • Referans2 Alp Tokat, T., Turkmenoglu, B., Guzel, Y., Kizilcan, D. S. 2019. “Investigation of 3D Pharmacophore Of N-benzyl Benzamide Molecules of Melanogenesis Inhibitors Using a New Descriptor Klopman Index: Uncertainties in Model”, J Mol Model, 25(8), 247.
  • Referans3 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y. 1987. “The Electron-Topological Approach in Investigation of Structure - Activity Relation - Inhibition of Thymidine Phosphorylase by Uracil Derivatives”, Bioorg Khim+, 13, 38-44.
  • Referans4 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y., Greni, A. I., Vysotskaya, L. E., Mikhailova, T. V. 1989 “Study Of The Electronic And Structural-Properties Of The Chemical-Compounds İn Garlic Aroma”, Nahrung, 33, 405-411.
  • Referans5 Bersuker, I. B., Dimoglo, A. S., Gorbachov, M. Y., Vlad, P. F. 1991. “Origin of Musk Fragrance Activity - the Electron-Topologic Approach”, New J Chem, 15, 307-320.
  • Referans6Biava, M., Porretta, G. C., Poce, G., Battilocchio, C., Alfonso, S., De Logu, A., Serra, N., Manetti, F., Botta, M. 2010. “Identification Of A Novel Pyrrole Derivative Endowed With Antimycobacterial Activity And Protection Index Comparable To That Of The Current Antitubercular Drugs Streptomycin And Rifampin”, Bioorg Med Chem, 18, 8076-8084.
  • Referans7 Consonni, V., Todeschini, R. 2010. “Molecular Descriptors”, Chall Adv Comput Che, 8, 29-102.
  • Referans8 Cramer, R. D., Patterson, D. E., Bunce, J. D. 1988. “Comparative Molecular-Field Analysis (Comfa) .1. Effect of Shape on Binding of Steroids to Carrier Proteins”, J Am Chem Soc, 110, 5959-5967.
  • Referans9 Dimoglo, A. S., Beda, A. A., Shvets, N. M., Gorbachov, M. Y., Kheifits, L. A., Aulchenko, I. S. 1995. “Investigation of the Relationship between Sandalwood Odor and Chemical-Structure - Electron-Topological Approach”, New J Chem, 19, 149-154.
  • Referans10 Dimoglo, A. S., Bersuker, I. B., Popa, D. P., Kuchkova, K. I. 1989. “The Electron-Topological Study of the Growth-Regulating Activity in a Series of Abscisic-Acid Analogs”, Teor Eksp Khim, 25, 590-594.
  • Referans11 Duncan, K., Barry, C. E. 2004. “Prospects For New Antitubercular Drugs”, Curr Opin Microbiol, 7, 460-465.
  • Referans12 Guzel, Y., Aslan, E., Turkmenoglu, B., Su, E. M. 2018. “4D-QSAR Studies Using a New Descriptor of the Klopman Index: Antibacterial Activities of Sulfone Derivatives Containing 1, 3, 4-Oxadiazole Moiety Based on MCET Model”, Curr Comput-Aid Drug, 14, 207-220.
  • Referans13 Hong, X., Hopfinger, A. J. 2003. “3D-Pharmacophores of Flavonoid Binding at the Benzodiazepine GABA (A) Receptor Site Using 4D-QSAR Analysis”, J Chem Inf Comp Sci, 43, 324-336.
  • Referans14 https://www.who.int/campaigns/world-tb-day/world-tb-day-2019, in.
  • Referans15 Joshi, S. D., More, U. A., Dixit, S. R., Korat, H. H., Aminabhavi, T. M., Badiger, A. M. 2014. “Synthesis, Characterization, Biological Activity, and 3D-QSAR Studies on Some Novel Class of Pyrrole Derivatives as Antitubercular Agents”, Med Chem Res, 23, 1123-1147.
  • Referans16 Kamal, A., Ramakrishna, G., Nayak, V. L., Raju, P., Rao, A. V. S., Viswanath, A., Vishnuvardhan, M. V. P. S., Ramakrishna, S., Srinivas, G. 2012. “Design and Synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine Conjugates as Potential Anticancer Agents”, Bioorgan Med Chem, 20, 789-800.
  • Referans17 Kizilcan, D. S., Turkmenoglu, B., Guzel, Y. 2020. “The Use of the Klopman İndex as A New Descriptor for Pharmacophore Analysis on Strong Aromatase İnhibitor Flavonoids against Estrogen-Dependent Breast Cancer”, Struct Chem, 31, 1339-1351.
  • Referans18 Klebe, G., Abraham, U., Mietzner, T. 1994. “Molecular Similarity Indexes in a Comparative-Analysis (Comsia) of Drug Molecules to Correlate and Predict Their Biological-Activity”, J Med Chem, 37, 4130-4146.
  • Referans19 Klopman, G. (1968). Chemical reactivity and the concept of charge- and frontier-controlled reactions. Journal of the American Chemical Society, 90(2), 223-234.
  • Referans20 Klopman, G. (1984a). Citation Classic - Chemical-Reactivity and the Concept of Charge-Controlled and Frontier-Controlled Reactions. Current Contents/Engineering Technology & Applied Sciences(20), 16-16. Retrieved from <Go to ISI>://WOS:A1984SP75100001
  • Referans21 Klopman, G. (1984b). Citation Classic - Chemical-Reactivity and the Concept of Charge-Controlled and Frontier-Controlled Reactions. Current Contents/Physical Chemical & Earth Sciences(20), 16-16. Retrieved from <Go to ISI>://WOS:A1984SP74700001
  • Referans22 Kubinyi, H. 1988. “Free Wilson Analysis - Theory, Applications and Its Relationship to Hansch Analysis”, Quant Struct-Act Rel, 7, 121-133.
  • Referans23 Leszczynskı, J. (2010), “Recent Advances in QSAR Studies: Methods and Applications, Chall Adv Comput Che, 8”, Springer Science+Business Media, Springer Dordrecht Heidelberg London New York, 1-423.
  • Referans24 LoPachin, R. M., Gavin, T. 2016. “Reactions Of Electrophiles With Nucleophilic Thiolate Sites: Relevance to Pathophysiological Mechanisms and Remediation”, Free Radical Res, 50, 195-205.
  • Referans25 Mohamed, M. S., Kamel, R., Fathallah, S. S. 2011. “Synthesis of New Pyrroles of Potential Anti-Inflammatory Activity”, Arch Pharm, 344, 830-839.
  • Referans26 Nantasenamat, C., Isarankura-Na-Ayudhya, C., Naenna, T., Prachayasittikul, V. 2009. “A Practical Overview of Quantitative Structure-Activity Relationship”, Excli J, 8, 74-88.
  • 27. Referans27 Nantasenamat, C., Isarankura-Na-Ayudhya, C., Prachayasittikul, V. 2010. “Advances in computational methods to predict the biological activity of compounds”, Expert Opin Drug Dis, 5 (2010) 633-654.
  • Referans28 Ragno, R., Marshall, G. R., Di Santo, R., Costi, R., Massa, S., Rompei, R., Artico, M. 2000. “Antimycobacterial Pyrroles: Synthesis, Anti-Mycobacterium Tuberculosis Activity and QSAR Studies”, Bioorgan Med Chem, 8, 1423-1432.
  • Referans29 Randic, M. 1996. “Molecular bonding profiles”, J Math Chem, 19, 375-392.
  • Referans30 Salem, L. 1968. “Intermolecular Orbital Theory of the İnteraction between Conjugated Systems. I. General Theory”, J Am Chem Soc, 90, 543-552.
  • Referans31 Saripinar, E., Guzel, Y., Patat, S., Yildirim, I., Akcamur, Y., Dimoglo, A. S. 1996. “Electron-Topological Investigation of the Structure-Antitubercular Activity Relationship of Thiosemicarbazone Derivatives”, Arzneimittel-Forschung/Drug Research, 46, 824-828.
  • Referans32 Sbardella, G., Mai, A., Artico, M., Loddo, R., Setzu, M. G., La Colla, P. 2004. “Synthesis and in Vitro Antimycobacterial Activity of Novel 3-(1H-pyrrol-1-yl)-2-oxazolidinone Analogues of PNU-100480”, Bioorg Med Chem Lett, 14, 1537-1541.
  • Referans33 Sippl, W, 2010. “3D-QSAR-Applications, Recent Advances, and Limitations”, Chall Adv Comput Che, 8, (ed., Puzyn, T., Leszczynski, J., Cronin, M. T. D.), Springer Science+Business Media, Springer Dordrecht Heidelberg London New York, 103-125.
  • Referans34 Türkmenoğlu, B., and Güzel, Y. 2021. “Confirmation by molecular docking of the pharmacophore defined as 4D-QSAR using the MCET method for the 2-hydroxydiarylamide derivatives”, International Journal of Chemistry and Technology, 5(1), 11-25.
  • Referans35 Türkmenoğlu, B., and Güzel, Y. 2021. “Klopman Index: A New Descriptor Used In MCET For 3D/4D-QSAR Modeling”, Current Academic Studies in Science and Mathematics Sciences, Livre de Lyon, Lyon, 1-16.
  • Referans36 Turkmenoglu, B., Guzel, Y. 2018. “Molecular Docking And 4D-QSAR Studies of Metastatic Cancer Inhibitor Thiazoles”, Comput Biol Chem, 76, 327-337. Referans37 Turkmenoglu, B., Guzel, Y., Su, E. M., Kizilcan, D. S. 2020. “Investigation Of İnhibitory Activity Of Monoamine Oxidase A With 4D-QSAR Using Fukui İndices İdentifier”, Mater Today Commun, 25, 1-6.
  • Referans38 Türkmenoglu, B., Yilmaz, H., Su, E. M., Alp Tokat, T., Güzel, Y. 2017. “4D-QSAR Study of Flavonoid Derivatives With MCET Method, International Journal of Chemistry and Technology, 1, 14-23.
  • Referans39 Yilmaz, H., Boz, M., Turkmenoglu, B., Guzel, Y. 2014. “Pharmacophore and Functional Group Identification of 4, 4’-dihydroxydiphenylmethane as Bisphenol-A (BSA) Derivative”, Trop J Pharm Res, 13, 117-126.
  • Referans40 Yilmaz, H., Guzel, Y., Onal, Z., Altiparmak, G., Kocakaya, S. O. 2011. “4D-QSAR Study of p56 (lck) Protein Tyrosine Kinase Inhibitory Activity of Flavonoid Derivatives Using MCET Method”, B Korean Chem Soc, 32, 4352-4360.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Dilek Şeyma Kızılcan 0000-0002-5695-7480

Burçin Türkmenoğlu 0000-0002-5770-0847

Yahya Güzel 0000-0002-4698-1866

Ertuğrul Aslan 0000-0002-0145-7876

Yayımlanma Tarihi 27 Mart 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 15 Sayı: 1

Kaynak Göster

APA Kızılcan, D. Ş., Türkmenoğlu, B., Güzel, Y., Aslan, E. (2022). 4D-QSAR Analysis of Some New Pyrrole Derivatives Using Klopman Index Descriptor. Erzincan University Journal of Science and Technology, 15(1), 168-182. https://doi.org/10.18185/erzifbed.973326