School Of Basic And Applied Sciences

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Author: search.filters.author.Haque, Shafiul

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    Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances
    (Academic Press Inc., 2023-06-20T00:00:00) Hussain, Arif; Kumar, Ajay; Uttam, Vivek; Sharma, Uttam; Sak, Katrin; Saini, Reena V.; Saini, Adesh K.; Haque, Shafiul; Tuli, Hardeep Singh; Jain, Aklank; Sethi, Gautam
    Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy. � 2023 Elsevier Inc.
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    Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation
    (MDPI, 2022-03-30T00:00:00) Rana, Nilottam; Singh, Atul Kumar; Shuaib, Mohd; Gupta, Sanjay; Habiballah, Mahmoud M.; Alkhanani, Mustfa F.; Haque, Shafiul; Reshi, Mohd Salim; Kumar, Shashank
    Drug-resistance-associated mutation in essential proteins of the viral life cycle is a major concern in anti-retroviral therapy. M46I, a non-active site mutation in HIV-1 protease has been clinically associated with saquinavir resistance in HIV patients. A 100 ns molecular dynamics (MD) simulation and MM-PBSA calculations were performed to study the molecular mechanism of M46I-mutation-based saquinavir resistance. In order to acquire deeper insight into the drug-resistance mechanism, the flap curling, closed/semi-open/open conformations, and active site compactness were studied. The M46I mutation significantly affects the energetics and conformational stability of HIV-1 protease in terms of RMSD, RMSF, Rg, SASA, and hydrogen formation potential. This mutation significantly decreased van der Waals interaction and binding free energy (?G) in the M46I�saquinavir complex and induced inward flap curling and a wider opening of the flaps for most of the MD simulation period. The predominant open conformation was reduced, but inward flap curling/active site compactness was increased in the presence of saquinavir in M46I HIV-1 protease. In conclusion, the M46I mutation induced structural dynamics changes that weaken the protease grip on saquinavir without distorting the active site of the protein. The produced information may be utilized for the discovery of inhibitor(s) against drug-resistant HIV-1 protease. � 2022 by the authors. Licensee MDPI, Basel, Switzerland.