Structural requirements of some derivatives based on natural alkaloid lycorine for their dengue inhibitory activity to accelerate dengue drug discovery efforts

Awasthi, Monika ; Amin, Sk. Abdul ; Shukla, Vijaya ; Jain, Sanskar ; Patil, Umesh Kumar; Gayen, Shovanlal

Abstract

Dengue virus (DENV) is one of the life threatening problems in tropical countries including India. During the last few decades, 50-100 million dengue viral infections were reported specially in Asia and Pacific region. In search of novel DENV inhibitor, the present study tried to correlate the DENV inhibitory data with a series of natural alkaloid lycorine derivatives. A statistically robust QSAR model is generated [R = 0.944; = 0.865; Q2 = 0.741; = 0.51593; = 0.826] with five descriptors such as GATS2c, ZMIC3, T_N_O_7, Quadrupole1 and nHsNH2. The reliability of the model was confirmed by Golbraikh and Tropsha acceptable model criteria. The QSAR result suggests that the hydroxyl group as well as linear aliphatic at R1 position is very important for the biological potency, whereas, amino and ether substituent at the R2 is detrimental. The study also revealed that bulky esterification at the R2 is not tolerable. Additionally, lead molecule showed good absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The findings may be useful to design potent lycorine-based anti-dengue compounds in future.


Keyword(s)

ADMET, Dengue, Lycorine, MLR, Natural alkaloid, NS4A, QSAR.

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