Faculty of Applied Sciences
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Item Targeting the DNA damage response machinery for lung cancer treatment(MDPI AG, 2022) Venugopala, Katharigatta N.Lung cancer is considered the most commonly diagnosed cancer and one of the leading causes of death globally. Despite the responses from small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients to conventional chemo- and radiotherapies, the current outcomes are not satisfactory. Recently, novel advances in DNA sequencing technologies have started to take off which have provided promising tools for studying different tumors for systematic mutation discovery. To date, a limited number of DDR inhibition trials have been conducted for the treatment of SCLC and NSCLC patients. However, strategies to test different DDR inhibitor combinations or to target multiple pathways are yet to be explored. With the various biomarkers that have either been recently discovered or are the subject of ongoing investigations, it is hoped that future trials would be designed to allow for studying targeted treatments in a biomarker-enriched population, which is defensible for the improvement of prognosis for SCLC and NSCLC patients. This review article sheds light on the different DNA repair pathways and some of the inhibitors targeting the proteins involved in the DNA damage response (DDR) machinery, such as ataxia telangiectasia and Rad3-related protein (ATR), DNA-dependent protein kinase (DNA-PK), and poly-ADP-ribose polymerase (PARP). In addition, the current status of DDR inhibitors in clinical settings and future perspectives are discussed.Item Current strategies in targeted anticancer drug delivery systems to brain(Elsevier, 2021) Bania, Ratnali; Borah, Pobitra; Deka, Satyendra; Dahabiyeh, Lina A.; Singh, Vinayak; Al-Shar’i, Nizar A.; Nair, Anroop B.; Goyal, Manoj; Venugopala, Katharigatta N.; Tekade, Rakesh Kumar; Deb, Pran Kishore; Dua, Kamal; Mehta, Meenu; de Jesus Andreoli Pinto, Terezinha; Pont, Lisa; Williams, Kylie; Rathbone, MichaelAdvanced Drug Delivery Systems in the Management of Cancer discusses recent developments in nanomedicine and nano-based drug delivery systems used in the treatment of cancers affecting the blood, lungs, brain, and kidneys. The research presented in this book includes international collaborations in the area of novel drug delivery for the treatment of cancer. Cancer therapy remains one of the greatest challenges in modern medicine, as successful treatment requires the elimination of malignant cells that are closely related to normal cells within the body. Advanced drug delivery systems are carriers for a wide range of pharmacotherapies used in many applications, including cancer treatment. The use of such carrier systems in cancer treatment is growing rapidly as they help overcome the limitations associated with conventional drug delivery systems. Some of the conventional limitations that these advanced drug delivery systems help overcome include nonspecific targeting, systemic toxicity, poor oral bioavailability, reduced efficacy, and low therapeutic index. This book begins with a brief introduction to cancer biology. This is followed by an overview of the current landscape in pharmacotherapy for the cancer management. The need for advanced drug delivery systems in oncology and cancer treatment is established, and the systems that can be used for several specific cancers are discussed. Several chapters of the book are devoted to discussing the latest technologies and advances in nanotechnology. These include practical solutions on how to design a more effective nanocarrier for the drugs used in cancer therapeutics. Each chapter is written with the goal of informing readers about the latest advancements in drug delivery system technologies while reinforcing understanding through various detailed tables, figures, and illustrations. Advanced Drug Delivery Systems in the Management of Cancer is a valuable resource for anyone working in the fields of cancer biology and drug delivery, whether in academia, research, or industry. The book will be especially useful for researchers in drug formulation and drug delivery as well as for biological and translational researchers working in the field of cancer.Item Crystallography, molecular modeling, and COX-2 inhibition studies on indolizine derivatives(MDPI AG, 2021-06) Venugopala, Katharigatta N.; Chandrashekharappa, Sandeep; Tratrat, Christophe; Deb, Pran Kishore; Nagdeve, Rahul D.; Nayak, Susanta K.; Morsy, Mohamed A.; Borah, Pobitra; Mahomoodally, Fawzi M.; Mailavaram, Raghu Prasad; Attimarad, Mahesh; Aldhubiab, Bandar E.; Sreeharsha, Nagaraja; Nair, Anroop B.; Alwassil, Osama I.; Haroun, Michelyne; Mohanlall, Viresh; Shinu, Pottathil; Venugopala, Rashmi; Kandeel, Mahmoud; Nandeshwarappa, Belakatte P.; Ibrahim, Yasmine F.The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.Item Crystallography, in silico studies, and In vitro antifungal studies of 2,4,5 trisubstituted 1,2,3-triazole analogues(MDPI AG, 2020-06-20) Venugopala, Katharigatta N.; Khedr, Mohammed A.; Girish, Yarabahally R.; Bhandary, Subhrajyoti; Chopra, Deepak; Morsy, Mohamed A.; Aldhubiab, Bandar E.; Deb, Pran Kishore; Attimarad, Mahesh; Nair, Anroop B.; Sreeharsha, Nagaraja; V, Rashmi; Kandeel, Mahmoud; Akrawi, Sabah H.; Reddy M B, Madhusudana; Shashikanth, Sheena; Alwassil, Osama I.; Mohanlall, VireshA series of 2,4,5 trisubstituted-1,2,3-triazole analogues have been screened for their antifungal activity against five fungal strains, Candida parapsilosis, Candida albicans, Candida tropicalis, Aspergillus niger, and Trichophyton rubrum, via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) microdilution assay. Compounds GKV10, GKV11, and GKV15 emerged as promising antifungal agents against all the fungal strains used in the current study. One of the highly active antifungal compounds, GKV10, was selected for a single-crystal X-ray diffraction analysis to unequivocally establish its molecular structure, conformation, and to understand the presence of different intermolecular interactions in its crystal lattice. A cooperative synergy of the C-H···O, C-H···N, C-H···S, C-H···π, and π···π intermolecular interactions was present in the crystal structure, which contributed towards the overall stabilization of the lattice. A molecular docking study was conducted for all the test compounds against Candida albicans lanosterol-14α-demethylase (pdb = 5 tzl). The binding stability of the highly promising antifungal test compound, GKV15, from the series was then evaluated by molecular dynamics studies.