In vitro cytotoxicity and druglikeness of pyrazolines and pyridines bearing benzofuran moiety

Asma S. Al Wasidi1, Ashraf S. Hassan2*, Ahmed M. Naglah3,4 1Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia. 2Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt. 3 Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair DEDC, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. 4 Peptide Chemistry Department, National Research Centre, 12622-Dokki, Cairo, Egypt.


Physicochemical properties and druglikeness
We predicted the physicochemical properties and druglikeness of the compounds (M1-M10) by using the SwissADME website (http://swissadme.ch).
The physicochemical properties give a global description of the structures of compounds (M1-M10) including molecular weight, molecular refractivity, topological polar surface area, number of rotatable bonds, heavy atoms, and hydrogen bond acceptors and donors ( Table 2).
The bioavailability radar of the compounds for six physicochemical properties is shown in Figure 2. The pink area represents the optimal range of these properties (Lovering et al., 2009;Ritchie et al., 2011), and the red line represents the properties of pyrazolines (M1-M8) and pyridines (M9 and M10).
In Figure 2, the red lines of four compounds (M1, M3, M4, and M6) are in the range of the pink area. Therefore, we can conclude that these compounds are predicted orally bioavailable.

5)
Muegge's filter includes 200 ≤ molecular weight ≤ 600, −2 ≤ XLOGP3 (lipophilicity) ≤ 5, the total polar surface area ≤ 150, the number of rings ≤ 7, the number of carbon > 4, the number of heteroatoms > 1, the number of rotatable bonds ≤15, the hydrogen bond acceptors ≤ 10, and the hydrogen bond donors ≤ 5 (Muegge et al., 2001). The result of drug-likeness evaluation of pyrazolines (M1-M8) and pyridines (M9 and M10) is shown in Table 3, and we can conclude that: • All the compounds, pyrazolines (M1-M8) and pyridines (M9 and M10), are in agreement with the Lipinski's rule. • According to Ghose's rule, all the compounds pass this rule excluding the two pyrazoline compounds (M7 and M8) due to the molar refractivity more than 130. • In the cases of Veber's rule and Egan's rule, all the compounds are in agreement with the two rules excluding one compound, pyridine M10, due to the total polar surface area more than 140 and 131.6, respectively. • According to Muegge's rule, all the compounds are in agreement with this rule excluding pyrazoline M8 due to its lipophilicity (XLOGP3) more than 5.

CONCLUSION
In this work, a series of pyrazolines M1-M8 and pyridines M9 and M10 were synthesized for the evaluation of their in vitro cytotoxic activities against two cell lines such as MCF-7 and HepG2. In general, some of pyrazolines and pyridines displayed cytotoxicity. Furthermore, the drug-likeness study revealed that most of the compounds fulfill the requirements of Lipinski, Ghose, Veber, Egan, and Muegge rules, and four compounds (M1, M3, M4, and M6) are predicted orally bioavailable. These preliminary results provide the lead for the design of more potent and selective anticancer drugs.