In Silico ADME Screening and Evaluation of Antimicrobial and Antimycobacterial Activities of 3,5-Diphenyl Pyrazoline Derivatives

Abstract

Objective: The unconscious widespread use of antibiotics leads to the development of resistance to antibiotics. When resistance to an antibiotic develops, it now either shows less efficacy or loses its effect completely at that antibiotic treatment dose. While the development of resistance to antibiotics increases rapidly, the need for the development of new antibiotics rises every day. For this purpose, in this study, antimicrobial and antitubercular effects of some compounds in the pyrazoline structure were investigated. The physicochemical properties and drug-likeness of the compounds are quite important for determining whether a compound can be used as a drug or not. Physicochemical properties and drug-likeness of the synthesized compounds were evaluated and the relevance for Lipinski’s rules was determined. Material-Method: Drug-likeness properties of the synthesized compounds were determined using online Swiss ADME tool. Antitubercular activity is detected by microplate alamar blue assay. Antimicrobial activity is tested by microdilution method. Results: All compounds obeyed the Lipinski’s rules, some of with no violation, some of with one violation. Compounds B7, B10 and B11 provided Lipinski’s rules with one violation. Other compounds ensured Lipinski’s rules with no violation. All compounds were predicted to have high gastrointestinal absorption. As the compounds generally have high lipophilicity, it was predicted that all compounds except B12 can cross the blood brain barrier. Conclusion: Synthesized compounds were mostly found to be more effective against Enterococcus faecalis, Enterococcus faecalis isolate and Candida albicans. Compound B10 demonstrated the best antimicrobial activity against Enterococcus faecalis isolate with a 16µg/mL MIC value. 

Keywords

• Pyrazoline
• antimycobacterial
• antimicrobial
• in silico ADME

Synthesis of 3,5-Diphenyl Pyrazoline Derivatives, In Silico ADME Screening, Evaluation of Antimicrobial and Antimycobacterial Activities

Abstract

Özet Amaç: Antibiyotiklere direnç gelişimi hızla artarken, her geçen gün yeni antibiyotik geliştirme ihtiyacı da artmaktadır. Bu amaçla, bu çalışmada pirazolin yapısındaki bazı bileşiklerin antimikrobiyal ve antitüberküloz etkileri araştırılmıştır. Bileşiklerin fizikokimyasal özellikleri ve ilaç özelliklerine benzerliği, bir bileşiğin ilaç olarak kullanılıp kullanılamayacağını belirlemek için oldukça önemlidir. Sentezlenen bileşiklerin fizikokimyasal özellikleri, ilaç özelliklerine benzerliği ve Lipinski kurallarına uygunluğu belirlendi. Materyal-Metod: Sentezlenen bileşiklerin ilaç özelliklerine benzerliği çevrimiçi İsviçre ADME aracı kullanılarak belirlendi. Antitüberküloz aktivite, mikroplaka alamar mavisi deneyi ile saptandı. Antimikrobiyal aktivite mikrodilüsyon yöntemi ile test edildi. Bulgular: Tüm bileşikler, bazıları hiç ihlal olmadan, bazıları da bir ihlalle Lipinski kurallarına uydu. B7, B10 ve B11 bileşikleri Lipinski'nin kurallarını bir ihlal ile sağlamıştır. Diğer bileşikler, Lipinski'nin kurallarının tamamını ihlalsiz olarak sağlamıştır. Tüm bileşiklerin yüksek gastrointestinal absorbsiyona sahip olduğu tahmin edildi. Bileşikler genel olarak yüksek lipofilisiteye sahip olduğundan, B12 dışındaki tüm bileşiklerin kan beyin bariyerini geçebileceği tahmin edildi. Sonuç: Sentezlenen bileşiklerin çoğunlukla Enterococcus faecalis, Enterococcus faecalis izolatı ve Candida albicans'a karşı daha etkili olduğu bulunmuştur. Bileşik B10, 16µg/mL MIC değeri ile Enterococcus faecalis izolatına karşı en iyi antimikrobiyal aktiviteyi sergilemiştir. Anahtar kelimeler: Pirazolin, antimikobakteriyel, antimikrobiyal, in siliko ADME Abstract Objective: While the development of resistance to antibiotics increases rapidly, the need for the development of new antibiotics rises every day. For this purpose, in this study, antimicrobial and antitubercular effects of some compounds in the pyrazoline structure were investigated. The physicochemical properties and drug-likeness of the compounds are quite important for determining whether a compound can be used as a drug or not. Physicochemical properties and drug-likeness of the synthesized compounds were evaluated and the relevance for Lipinski’s rules was determined. Material-Method: Drug-likeness properties of the synthesized compounds were determined using online Swiss ADME tool. Antitubercular activity is detected by microplate alamar blue assay. Antimicrobial activity is tested by microdilution method. Results: All compounds obeyed the Lipinski’s rules, some of with no violation, some of with one violation. Compounds B7, B10 and B11 provided Lipinski’s rules with one violation. Other compounds ensured Lipinski’s rules with no violation. All compounds were predicted to have high gastrointestinal absorption. As the compounds generally have high lipophilicity, it was predicted that all compounds except B12 can cross the blood brain barrier. Conclusion: Synthesized compounds were mostly found to be more effective against Enterococcus faecalis, Enterococcus faecalis isolate and Candida albicans. Compound B10 demonstrated the best antimicrobial activity against Enterococcus faecalis isolate with a 16µg/mL MIC value. Keywords: Pyrazoline, antimycobacterial, antimicrobial, in silico ADME

Keywords

• Pyrazoline
• antimycobacterial
• antimicrobial
• in silico ADME

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