Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species

Shahzad Saleem; Shabana Bibi; Qudsia Yousafi; Tehzeem Hassan; Muhammad Saad Khan; Mohammad Mehedi Hasan; Hitesh Chopra; Mahmoud Moustafa; Mohammed Al-Shehri; Mohammad Khalid; Atul Kabra

doi:10.1155/2022/7040547

Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species

Evid Based Complement Alternat Med. 2022 Jun 8:2022:7040547. doi: 10.1155/2022/7040547. eCollection 2022.

Authors

Affiliations

¹ COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan.
² Department of Biological Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
³ Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming 10, Yunnan 650091, China.
⁴ Department of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh.
⁵ Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
⁶ Department of Biology, College of Science, King Khalid University, Abha 9004, Saudi Arabia.
⁷ Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena, Egypt.
⁸ Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁹ University Institute of Pharma Sciences, Chandigarh University, Ghruan, Mohali 140413, Punjab, India.

Abstract

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of β-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for β-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å². log P < 5 was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between -9.2 and -4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.